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1.
J. Wischhusen  F. Padilla 《IRBM》2019,40(1):10-15

Background

Ultrasound-targeted microbubble destruction (UTMD) is a type of ultrasound therapy, in which low frequency moderate power ultrasound is combined with microbubbles to trigger cavitation. Cavitation is the process of oscillation of gas bubbles causing biophysical effects such as pushing and pulling or shock waves that permeabilize biological barriers. In vivo, cavitation results in tissue permeabilization and is used to enable local delivery of nanomedicine. While cavitation can occur in biological liquids when high pressure ultrasound is applied, the use of microbubbles as cavitation nuclei in UTMD largely facilitates the induction of cavitation. UTMD is intensively studied for drug delivery into tumor tissue, but also for the activation of anti-tumor immune responses. The first clinical studies of UTMD-mediated chemotherapy delivery confirmed safety and efficacy of this approach.

Aim

The present review summarizes ultrasound settings, cavitation approaches, biophysical mechanisms of drug delivery, drug carriers, and pre-clinical and clinical applications of UTMD for drug delivery into tumors.  相似文献   

2.
V. Sharma  K.C. Juglan 《IRBM》2018,39(5):313-323

Background

Fatty Liver Disease (FLD) is one of the most critical diseases that should be detected and cured at the earlier stage in order to decrease the mortality rate. To identify the FLD, ultrasound images have been widely used by the radiologists. However, due to poor quality of ultrasound images, they found difficulties in recognizing FLD. To resolve this problem, many researchers have developed various Computer Aided Diagnosis (CAD) systems for the classification of fatty and normal liver ultrasound images. However, the performance of existing CAD systems is not good in terms of sensitivity while classifying the FLD.

Methods

In this paper, an attempt has been made to present a CAD system for the classification of liver ultrasound images. For this purpose, texture features are extracted by using seven different texture models to represent the texture of Region of Interest (ROI). Highly discriminating features are selected by using Mutual Information (MI) feature selection method.

Results

Extensive experiments have been carried out with four different classifiers, and for carrying out this study, 90 liver ultrasound images have been taken. From the experimental results, it has been found that the proposed CAD system is able to give 95.55% accuracy and sensitivity of 97.77% with the 20 best features selected by the MI feature selection technique.

Conclusion

The experimental results show that the proposed system can be used for the classification of fatty and normal liver ultrasound images with higher accuracy.  相似文献   

3.
D. Koundal  S. Gupta  S. Singh 《IRBM》2018,39(1):43-53

Background

Neutrosophic based methods are becoming very popular in denoising of images due to the capability of handling indeterminacy. The main goal of denoising is to maintain balance between edge preservation and speckle reduction.

Methods

To achieve this, neutrosophic based total variation method using Nakagami statistics have been explored to develop an efficient speckle reduction method. The proposed Neutrosophic based Nakagami Total Variation (NNTV) method initially transforms the image into the neutrosophic domain and then employs the neutrosophic filtering process for speckle reduction. The NNTV quantifies the indeterminacy of image by determining the entropy of indeterminate set.

Results

The performance of the proposed method has been evaluated quantitatively by quality metrics on synthetic images, qualitatively using real thyroid ultrasound images through visual examination by medical experts and by Mean Opinion Score.

Conclusion

From results, it has been observed that NNTV method performed better than other speckle reduction methods in terms of both speckle suppression and edge preservation.  相似文献   

4.

Background

Interest in selenium research has considerably grown over the last decades owing to the association of selenium deficiencies with an increased risk of several human diseases, including cancers, cardiovascular disorders and infectious diseases. The discovery of a genetically encoded 21st amino acid, selenocysteine, is a fascinating breakthrough in molecular biology as it is the first addition to the genetic code deciphered in the 1960s. Selenocysteine is a structural and functional analog of cysteine, where selenium replaces sulfur, and its presence is critical for the catalytic activity of selenoproteins.

Scope of review

The insertion of selenocysteine is a non-canonical translational event, based on the recoding of a UGA codon in selenoprotein mRNAs, normally used as a stop codon in other cellular mRNAs. Two RNA molecules and associated partners are crucial components of the selenocysteine insertion machinery, the Sec-tRNA[Ser]Sec devoted to UGA codon recognition and the SECIS elements located in the 3′UTR of selenoprotein mRNAs.

Major conclusions

The translational UGA recoding event is a limiting stage of selenoprotein expression and its efficiency is regulated by several factors.

General significance

The control of selenoproteome expression is crucial for redox homeostasis and antioxidant defense of mammalian organisms. In this review, we summarize current knowledge on the co-translational insertion of selenocysteine into selenoproteins, and its layers of regulation.  相似文献   

5.

Background

Ultrasound plays an important role in cancer diagnosis. B-mode imaging and contrast-enhanced ultrasound are routinely used to detect cancerous lesions in breast and liver. The use of ultrasound contrast agents (UCAs) such as microbubbles (MBs), which can be functionalized with targeting ligands, has further enabled ultrasound molecular imaging (USMI) of specific molecular markers in pre-clinical and the first clinical studies. As targeted MBs have a diameter of 1–4 μm, they are limited to the blood vasculature upon intravenous injection, and can bind to markers of the vascular endothelium. USMI with targeted MBs was applied for imaging of markers of inflammation, angiogenesis, and the tumor endothelium.

Aim

The present review provides an introduction to USMI and presents currently available UCAs, targeting strategies, pre-clinical targets, proposed applications, and the first clinical studies with USMI to guide novel users and assess the technique's potential for clinical use.  相似文献   

6.

Background

Vitamin K (VK) is a fat-soluble vitamin known for its essential role in blood coagulation, but also on other biological processes (e.g. reproduction, brain and bone development) have been recently suggested. Nevertheless, the molecular mechanisms behind its particular function on reproduction are not yet fully understood.

Methods

The potential role of VK on reproduction through nutritional supplementation in Senegalese sole (Solea senegalensis) was assessed by gonadal maturation and 11-ketosterone, testosterone and estriol plasma levels when fed with control or VK supplemented (1250?mg?kg?1 of VK1) diets along a six month trial. At the end, sperm production and quality (viability and DNA fragmentation) were evaluated. Circulating small non-coding RNAs (sncRNAs) in blood plasma from males were also studied through RNA-Seq.

Results

Fish fed with dietary VK supplementation had increased testosterone levels and lower sperm DNA fragmentation. SncRNAs from blood plasma were found differentially expressed when nutritional and sperm quality conditions were compared. PiR-675//676//4794//5462 and piR-74614 were found up-regulated in males fed with dietary VK supplementation. Let-7g, let-7e(18nt), let-7a-1, let-7a-3//7a-2//7a-1, let-7e(23nt) and piR-675//676//4794//5462 were found to be up-regulated and miR-146a and miR-146a-1//146a-2//146a-3 down-regulated when fish with low and high sperm DNA fragmentation were compared. Bioinformatic analyses of predicted mRNAs targeted by sncRNAs revealed the potential underlying pathways.

Conclusions

VK supplementation improves fish gonad maturation and sperm quality, suggesting an unexpected and complex regulation of the nutritional status and reproductive performance through circulating sncRNAs.

General significance

The use of circulating sncRNAs as reliable and less-invasive physiological biomarkers in fish nutrition and reproduction has been unveiled.  相似文献   

7.

Background

Binding of chemokines to glycosaminoglycans (GAGs) is a crucial step in leukocyte recruitment to inflamed tissues.

Methods

A disaccharide compositional analysis of the HS dp6 fraction in combination with MS analysis of the CCL2-depleted dp6 fraction was the basis for target GAG ligand structure suggestions. Four experimentally-derived heparan sulfate hexasaccharides, two potentially chemokine-specific and two unspecific, have been docked to CCL2. Subsequent 300?ns molecular dynamics simulations were used to improve the docked complexes.

Results

Hexasaccharides with four sulfations and no acetylations are suggested for selective and high affinity chemokine binding. Using the Antithromin-III/heparin complex as positive control for docking, we were able to recover the correct complex structure only if the previously liganded ATIII structure was used as input. Since the liganded structure is not known for a CCL2-GAG complex, we investigated if molecular dynamics simulations could improve initial docking results. We found that all four GAG oligosaccharides ended up in close contact with the known binding residues after about 100?ns simulation time.

Conclusions

A discrimination of specific vs. unspecific CCL2 GAG ligands is not possible by this approach. Long-time molecular dynamics simulations are, however, well suited to capture the delicate enthalpy/entropy balance of GAG binding and improve results obtained from docking.

General significance

With the comparison of two methods, MS-based ligand identification and molecular modelling, we have shown the current limitations of our molecular understanding of complex ligand binding which is could be due to the numerical inaccessibility of ligand-induced protein conformational changes.  相似文献   

8.

Background

3D ultrasound volume reconstruction from B-model ultrasound slices can provide more clearly and intuitive structure of tissue and lesion for the clinician.

Methods

This paper proposes a novel Global Path Matching method for the 3D reconstruction of freehand ultrasound images. The proposed method composes of two main steps: bin-filling scheme and hole-filling strategy. For the bin-filling scheme, this study introduces two operators, including the median absolute deviation and the inter-quartile range absolute deviation, to calculate the invariant features of each voxel in the 3D ultrasound volume. And the best contribution range for each voxel is obtained by calculating the Euclidian distance between current voxel and the voxel with the minimum invariant features. Hence, the intensity of the filling vacant voxel can be obtained by weighted combination of the intensity distribution of pixels in the best contribution range. For the hole-filling strategy, three conditions, including the confidence term, the data term and the gradient term, are designed to calculate the weighting coefficient of the matching patch of the vacant voxel. While the matching patch is obtained by finding patches with the best similarity measure that defined by the three conditions in the whole 3D volume data.

Results

Compared with VNN, PNN, DW, FMM, BI and KR methods, the proposed Global Path Matching method can restore the 3D ultrasound volume with minimum difference.

Conclusions

Experimental results on phantom and clinical data sets demonstrate the effectiveness and robustness of the proposed method for the reconstruction of ultrasound volume.
  相似文献   

9.

Background

High levels of blood cholesterol are conventionally linked to an increased risk of developing cardiovascular disease (Grundy, 1986). Here we examine the molecular mode of action of natural products with known cholesterol-lowering activity, such as for example the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys.

Methods

Molecular Dynamics simulations are used to gain insight into the formation process of mixed micelles and, correspondingly, how active agents epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys could possibly interfere with it.

Results

Self-assembly of physiological micelles occurs on the order of 35–50?ns; most of the structural properties of mixed micelles are unaffected by epigallocatechin gallate or Ile-Ile-Ala-Glu-Lys which integrate into the micellar surface; the diffusive motion of constituting lipids palmitoyl-oleoyl-phosphatidylcholine and cholesterol is significantly down-regulated by both epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys;

Conclusions

The molecular mode of action of natural compounds epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys is a significant down-regulation of the diffusive motion of micellar lipids.

General significance

Natural compounds like the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys, lead to a significant down-regulation of the diffusive motion of micellar lipids thereby modulating cholesterol absorption into physiological micelles.  相似文献   

10.
S. Lee  J.S. Lee  J.P. Kim  K. Kim  C.H. Hwang  K.-i. Koo 《IRBM》2018,39(5):343-352

Background

Convenient and precise measurement of the Cobb angle using a small size X-ray detector has been required for local clinics.

Methods

Cobb angle measurement system using a conventional X-ray source and detector is proposed for accurate Cobb angle measurement. The system consists of a conventional X-ray source, a ruler-added X-ray table, a conventional X-ray detector, and an image processing program. The X-ray table has the lead ruler patterns. The patterns remain white ruler patterns on X-ray images. The proposed image processing program merges the three spinal X-ray images into one whole spinal X-ray image by detecting the ruler patterns on the three spinal X-ray images.

Results

In order to evaluate our program, Cobb angle measured in the merged image is compared with Cobb angle measured in the X-ray image taken by a large X-ray detector. Average of difference between them is 2.251 degree and standard deviation is 1.339.

Conclusion

The developed measurement system demonstrated its measurement performance accurately and practically.  相似文献   

11.

Background

Selenoproteins (25 genes in human) co-translationally incorporate selenocysteine using a UGA codon, normally used as a stop signal. The human selenoproteome is primarily regulated by selenium bioavailability with a tissue-specific hierarchy.

Methods

We investigated the hierarchy of selenoprotein expression in response to selenium concentration variation in four cell lines originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno-detection, (iv) selenium-specific mass spectrometric detection after non-radioactive 76Se labeling of selenoproteins, and (v) luciferase-based reporter constructs in various cell extracts.

Results

We characterized cell-line specific alterations of the selenoproteome in response to selenium variation that, in most of the cases, resulted from a translational control of gene expression. We established that UGA-selenocysteine recoding efficiency, which depends on the nature of the SECIS element, dictates the response to selenium variation.

Conclusions

We characterized that selenoprotein hierarchy is cell-line specific with conserved features. This analysis should be done prior to any experiments in a novel cell line.

General significance

We reported a strategy based on complementary methods to evaluate selenoproteome regulation in human cells in culture.  相似文献   

12.
13.

Background

We have previously demonstrated the neuroprotective activity of tetracycline on a Spinocerebellar Ataxia 3 nematode model. Here, we present the screening of a small library of tetracycline congeners in order to identify the most effective compound in preventing ataxin-3 aggregation.

Methods

We performed the assays on the Josephin Domain as it is directly involved in the onset of fibrillation. We used thioflavin T and solubility assays to spot out the most effective tetracycline congeners; Fourier transform infrared and NMR spectroscopies to characterize their mode of action. We employed an ataxic Caenorhabditis elegans model to evaluate the pharmacological efficacy of tetracycline congeners.

Results

Methacycline was identified as the most effective compound. Like tetracycline, methacycline neither significantly affected the aggregation kinetics nor did it change the secondary structures of the final aggregates but increased the solubility of the aggregated species. Saturation transfer NMR experiments demonstrated methacycline capability to only bind the oligomeric species of Josephin Domain. Competition assays also showed that methacycline binds to the Josephin Domain more tightly than tetracycline. The treatment with methacycline induced a significant improvement in motility and locomotion of the transgenic C. elegans without changing its lifespan. The efficacy was distinctly stronger than that of tetracycline. Noteworthy, unlike tetracycline, methacycline was able to retard aging-related decline in motility of even the healthy worms used.

Conclusions

The apparent absence of toxic effects displayed by methacycline, along with its stronger efficacy in contrasting expanded ataxin-3 toxicity, makes it a possible candidate for a chronic treatment of the disease.  相似文献   

14.

Background

Heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-O-sulfotransferases (HS3STs) in humans, still it is the rarest modification in HS and its biological function is yet misunderstood. HS3ST2 and HS3ST3B exhibit the same activity in vitro. They are however differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes. Here, we hypothesized that both isozymes might also display distinct subcellular localizations.

Methods

The subcellular distribution of HS3ST2 and HS3ST3B was analysed by using overexpression systems in HeLa cells. The localization of endogenous HS3ST2 was confirmed by immunostaining in primary macrophages.

Results

We found that HS3ST3B was only localized in the Golgi apparatus and no difference between full-length enzyme and truncated construct depleted of its catalytic domain was observed. In contrast, HS3ST2 was clearly visualized at the plasma membrane. Its truncated form remained in the Golgi apparatus, meaning that the catalytic domain might support correct addressing of HS3ST2 to cell surface. Moreover, we found a partial co-localization of HS3ST2 with syndecan-2 in HeLa cells and primary macrophages. Silencing the expression of this proteoglycan altered the localization of HS3ST2, which suggests that syndecan-2 is required to address the isozyme outside of the Golgi apparatus.

Conclusions

We demonstrated that HS3ST3B is a Golgi-resident isozyme, while HS3ST2 is addressed to the plasma membrane with syndecan-2.

General significance

The membrane localization of HS3ST2 suggests that this enzyme may participate in discrete processes that occur at the cell surface.  相似文献   

15.

Background

During the development of obesity the expansion of white adipose tissue (WAT) leads to a dysregulation and an excessive remodeling of extracellular matrix (ECM), leading to fibrosis formation. These ECM changes have high impact on WAT physiology and may change obesity progression. Blocking WAT fibrosis may have beneficial effects on the efficacy of diet regimen or therapeutical approaches in obesity. Since dipeptidyl peptidase IV (DPP-IV) inhibitors prevent fibrosis in tissues, such as heart, liver and kidney, the objective of this study was to assess whether vildagliptin, a DPP-IV inhibitor, prevents fibrosis in WAT in a mouse model of obesity, and to investigate the mechanisms underlying this effect.

Methods

We evaluated the inhibitory effect of vildagliptin on fibrosis markers on WAT of high-fat diet (HFD)-induced obese mice and on 3T3-L1 cell line of mouse adipocytes treated with a fibrosis inducer, transforming growth factor beta 1 (TGFβ1).

Results

Vildagliptin prevents the increase of fibrosis markers in WAT of HFD-fed mice and reduces blood glucose, serum triglycerides, total cholesterol and leptin levels. In the in vitro study, the inhibition of DPP-IV with vildagliptin, neuropeptide Y (NPY) treatment and NPY Y1 receptor activation prevents ECM deposition and fibrosis markers increase induced by TGFβ1 treatment.

Conclusions

Vildagliptin prevents fibrosis formation in adipose tissue in obese mice, at least partially through NPY and NPY Y1 receptor activation.

General significance

This study highlights the importance of vildagliptin in the treatment of fibrosis that occur in obesity.  相似文献   

16.

Background

DNMT3A, as de novo DNA methyltransferase, is essential for regulating gene expression through cellular development and differentiation. The functions of DNMT3A rely on its oligomeric states and allosteric regulations between its catalytic domain and binding partners. Despite recent resolution of autoinhibitory and active DNMT3A/3L crystal structures, the mechanism of their functional motions and interdomain allostery in regulating the activity remains to be established.

Methods

The hybrid approach, comprising Elastic Network Models coupled with information theory, Protein Structure Network, and sequence evolution analysis was employed to investigate intrinsic dynamics and allosteric properties of DNMT3A resolved in autoinhibitory and active states.

Results

The conformational transition between two states is characterized by global motions, and the homo-dimer displays the similar dynamic properties as tetramer, acting as the basic functional unit. The hinge residues with restricted fluctuations are clustered at the dimer interface, which are predicted to enjoy remarkably efficient signal transduction properties. The allosteric pathways through the dimer interface are achieved by a cascade of interactions predominantly involving conserved and co-evolved residues.

Conclusions

Our results suggest that structural topology coupled with global motions indicates the structural origin of the functional transformation of DNMT3A. The comprehensive analysis further highlights the pivotal role of the dimer interface of DNMT3A both in defining the quaternary structure dynamics and establishing interdomain communications.

General significance

Understanding the global motions of DNMT3As not only provides mechanical insights into the functions of such molecular machines, but also reveals the mediators that determine their allosteric regulations.  相似文献   

17.

Aim

To test the fitness-gain curve model proposes that cosexual plants adjust their sex ratios and resource allocation depending on their size. In this study, the monoecious species Sagittaria potamogetifolia was used as a model to determine the effects of plant size and density on gender modification and reproductive allocation.

Methods and materials

Various traits, including flower number and plant biomass, were measured under four different artificially constructed population density treatments. More male flowers were produced than female flowers per individual at high densities, while the opposite trend was observed at low densities. This trend was particularly evident in the highest density treatment.

Results

A trade-off was discovered between male–female sex allocations in the highest density treatment (40 individuals m?2). The allometric growth of reproductive organs compared with plant size was detected, as evidenced by the reproductive structures’ biomass and flower numbers. However, in the highest density treatment, size was weakly negatively correlated with femaleness.

Conclusion

Thus, S. potamogetifolia has a reproductive strategy that easily adjusts to different reproductive environmental densities.  相似文献   

18.

Background

Phasins are low molecular mass proteins that accumulate strongly in bacterial cells in response to the intracellular storage of polyhydroxyalkanoates (PHA). Although lacking catalytic activity, phasins are the major components of the surface of the PHA granules and could be potentially involved in the formation of a network-like protein layer surrounding the polyester inclusions. Structural models revealed phasins to possess coiled-coil regions that might be important in the establishment of protein-protein interactions. However, there is not experimental evidence of a coiled-coil mediated oligomerization in these proteins.

Methods

Structure prediction analyses were used to characterize the coiled-coil motifs of phasins PhaF and PhaI –produced by the model bacterium Pseudomonas putida KT2440–. Their oligomerization was evaluated by biolayer interferometry and the in vivo two-hybrid (BACTH) system. The interaction ability of a series of coiled-coil mutated derivatives was also measured.

Results

The formation of PhaF and PhaI complexes was detected. A predicted short leucine zipper-like coiled-coil (ZIP), containing “ideal” residues located within the hydrophobic core, was shown responsible for the oligomers stability. The substitution of key residues (leucines or valines) in PhaI ZIP (ZIPI) for alanine reduced by four fold the oligomerization efficiency.

Conclusions

These results indicate that coiled-coil motifs are essential for phasin interactions. Correct oligomerization requires the formation of a stable hydrophobic interface between both phasins.General Significance.Our findings elucidate the oligomerization motif of PhaF and PhaI. This motif is present in most phasins from PHA-accumulating bacteria and offers a potentially important target for modulating the PHA granules stability.  相似文献   

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