A label-free electrochemical biosensor based on 3D cubic Eu3+/Cu2O nanostructures with clover-like faces for the determination of anticancer drug cytarabine

The present research utilized a simplified procedure for developing a novel electro-chemical DNA biosensor based on a carbon paste electrode (CPE) modified with three-dimensional (3D) cubic Eu³⁺/Cu₂O nanostructures with clover-like faces (Eu³⁺/Cu₂O CLFNs). The modified electrode was applied to monitor electro-chemical interactions between dsDNA and cytarabine for the first time. Then, the decreased oxidation signal of guanine following the interactions between cytarabine and dsDNA was utilized as an indicator for selectively determining cytarabine using differential pulse voltammetry (DPV). According to the findings, the oxidation peak current of guanine was linearly proportionate with the cytarabine concentration in the range between 0.01 and 90 μM. Additionally, the limit of quantification (LOQ) and the limit of detection (LOD) respectively equaled 9.4 nM and 2.8 nM. In addition, the repeatability, applicability and reproducibility of this analysis to drug dosage forms and human serum samples were investigated. Furthermore, UV-vis spectroscopy, DPV, docking and viscosity measurements were applied to elucidate the interaction mechanism of dsDNA with cytarabine. It was found that this DNA biosensor may be utilized to sensitively, accurately and rapidly determine cytarabine.

Electrochemical biosensor based on three-dimensional (3D) cubic of Eu³⁺/Cu₂O with clover-like face nano-structures and ds-DNA modified carbon paste electrode for detecting cytarabine was fabricated.     

The effects of orbit type on synthetic aperture RADAR (SAR) backscatter

The difference between an image pair acquired in crossing orbits of Synthetic Aperture Radar (SAR) sensors is of great importance. In this study, this difference was investigated in terms of backscatter and scattering mechanisms for several classes, including the Ground Vegetation (Gv), Water (Wtr), and Trees. Two RADARSAT-2 image pairs were used, one in spring and the other in winter. Almost all conditions were similar for each image pair except for the type of orbit. In the spring image pair, the backscatter for almost all classes from the image in the ascending orbit was more than that from the image captured in the descending mode. This was attributed to the change in the amount of evapotranspiration and the water content for the Gv and Tree classes, and was the result of wind speed variation for the Wtr class. For the winter image pair however, no significant difference was observed between the images acquired in the crossing orbits. The reason was that all the classes were frozen and, therefore, no evapotranspiration and roughness change occurred in that time. The results of this study proved that the difference between the images captured from crossing SAR orbits should be taken into account.     

Mammalian sperm hyperactivation regulates navigation via physical boundaries and promotes pseudo-chemotaxis

Mammalian sperm migration within the complex and dynamic environment of the female reproductive tract toward the fertilization site requires navigational mechanisms, through which sperm respond to the tract environment and maintain the appropriate swimming behavior. In the oviduct (fallopian tube), sperm undergo a process called “hyperactivation,” which involves switching from a nearly symmetrical, low-amplitude, and flagellar beating pattern to an asymmetrical, high-amplitude beating pattern that is required for fertilization in vivo. Here, exploring bovine sperm motion in high–aspect ratio microfluidic reservoirs as well as theoretical and computational modeling, we demonstrate that sperm hyperactivation, in response to pharmacological agonists, modulates sperm–sidewall interactions and thus navigation via physical boundaries. Prior to hyperactivation, sperm remained swimming along the sidewalls of the reservoirs; however, once hyperactivation caused the intrinsic curvature of sperm to exceed a critical value, swimming along the sidewalls was reduced. We further studied the effect of noise in the intrinsic curvature near the critical value and found that these nonthermal fluctuations yielded an interesting “Run–Stop” motion on the sidewall. Finally, we observed that hyperactivation produced a “pseudo-chemotaxis” behavior, in that sperm stayed longer within microfluidic chambers containing higher concentrations of hyperactivation agonists.

The navigational mechanisms that regulate sperm migration through the complex and dynamic physical and chemical environments of the female reproductive tract to the site of fertilization are poorly understood (1, 2). Over many years, studies have revealed that the biophysical navigational cues for sperm in the female tract include fluid flow (3–7), wall architecture (8–12), ambient rheological properties such as fluid viscoelasticity (13), and possible temperature gradients (14, 15). There is also evidence that biochemical cues from the female tract serve to modulate sperm migration (16). These may include chemoattractants (17, 18), molecular triggers that change sperm flagellar beating patterns (19–21), and sperm receptors on the epithelium of the tract that anchor sperm (22–24).The in vivo biochemical factors that transform sperm flagellar beating patterns are not precisely known (16), but in vitro exposure to certain chemical stimuli results in similar transformation of the flagellar beating pattern (25). Specifically, exposure to certain chemical stimuli results in the rise of cytoplasmic Ca²⁺ in sperm (26, 27) through either activation of CATSPER membrane ion channels and flux of exogenous Ca²⁺ ions into the flagellum (28, 29) or by mobilization of intracellular Ca²⁺ stores (30–32) or both. In turn, this rise of cytoplasmic Ca²⁺ concentration results in an increase of asymmetry in the flagellar beat cycle. This process is called “hyperactivation,” and it is required for fertilization (33, 34), as it enhances the ability of sperm to penetrate the matrix of the oocyte’s cumulus oophorus and zona pellucida to reach the plasma membrane of the oocyte (21). Furthermore, there is evidence that hyperactivation assists sperm swimming through viscoelastic substances in the female reproductive tract (35) and plays a role in detaching sperm from epithelial cells in the oviduct (36). It has been observed that hyperactivation is stimulated via a concentration-dependent mechanism (21).Although past findings have revealed roles that hyperactivation plays in supporting the success of fertilization, it remains elusive whether this functional state of motility is directly involved in sperm navigation within the female reproductive tract. Accordingly, we hypothesized that hyperactivation influences sperm–sidewall interactions and thus regulates sperm navigation via nearby wall architecture. Furthermore, we expected this regulatory mechanism to be dependent on the concentration of hyperactivation agonists.Here, using microfluidic experimentation with bovine sperm as well as theoretical and computational modeling, we investigated the effect of hyperactivation on hydrodynamic sperm–sidewall interactions in both standard and viscoelastic media. We used two established pharmacological agents to trigger hyperactivation in sperm: caffeine (25) and 4-aminopyridine (4-AP) (37). We demonstrated that hyperactivation directly regulates sperm interactions with sidewalls of our microfluidic reservoirs and thus navigation via physical boundaries. As a result of this concentration-dependent regulatory mechanism, we observed a “pseudo-chemotaxis” phenomenon in which sperm accumulated within reservoirs with higher concentrations of hyperactivation agonists. Our results revealed a potential role of hyperactivation in the navigational response of sperm to biochemical cues within the female reproductive tract.     

Microfluidic synthesis of PLGA/carbon quantum dot microspheres for vascular endothelial growth factor delivery

In this study, vascular endothelial growth factor (VEGF) loaded poly(d,l-lactide-co-glycolide) (PLGA) – carbon quantum dot microspheres were produced using microfluidic platforms. The microcapsules were fabricated in flow-focusing geometry with a biphasic flow to generate solid/oil/water (s–o–w) droplets. To avoid any damage to protein functional and structural stability during the encapsulation process, the VEGF was PEGylated. The produced microspheres were intact and highly monodisperse in size (CV < 5%). Furthermore, microspheres in a size range of 16–36 µm were achieved by adjusting the flow ratio parameter. The encapsulation efficiency, release profile, and bioactivity of the produced microparticles were also studied. The loading efficiency of PEGylated VEGF in the microparticles was varied from 51–69% and more than 90% of PEGylated VEGF was released within 28 days. Furthermore, the release of VEGF was indirectly monitored by carbon quantum dots. The present monodisperse and controllable VEGF loaded microspheres with reproducible manner could be widely used in tissue engineering and therapeutic applications.

In this study, vascular endothelial growth factor (VEGF) loaded poly(d,l-lactide-co-glycolide) (PLGA) – carbon quantum dot microspheres were produced using microfluidic platforms.     

Physiological Temperature Has a Crucial Role in Amyloid Beta in the Absence and Presence of Hydrophobic and Hydrophilic Nanoparticles

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Genetic Variation and Selection of Domain I of the Plasmodium vivax Apical Membrane Antigen-1(AMA-1) Gene in Clinical Isolates from Iran

Background

Apical Membrane antigen 1 (AMA-1) is positioned on the surface of merozoite and it may play a role in attack to red blood cells. The main aim of present study was to determine the genetic variation, as well as, to detect of selection at domain I of AMA-1 gene Plasmodium vivax isolates in Iran.

Methods

Blood samples were collected from 58 patients positive for P. vivax, mono infection and the domain I of AMA-1 gene was amplified by nested PCR and then sequenced.

Results

A total 33 different haplotypes were identified among 58 Iranian sequences. The 23 new haplotypes were determined in this study that was not reported previously in other regions of the world. There were totally observed 36 point mutations at the nucleotide level in the analyzed sequences. Sequences analyses indicated 25 amino acid changes at 20 positions in which 5 sites demonstrated thrimorphic polymorphism and the others were dimorphic in the domain I of the Iranian PvAMA-1 isolates.

Conclusion

Our findings indicated relatively high level of allelic diversity at the domain I of PvAMA-1 among P.vivax isolates of Iran. Since, PvAMA-1 is considering as vaccine candidate antigen, these data provide valuable information for the development of a PvAMA-1 based malaria vaccine.     

Efficacy of 2% metronidazole gel in moderate acne vulgaris

Background:

Acne vulgaris is an inflammatory disease of the pilosebaceous units. Various systemic and topical options are available for its treatment.

Aims:

This study aimed to evaluate the efficacy of 2% metronidazole gel in acne vulgaris.

Materials and Methods:

Double-blind, randomized, placebo-controlled, split-face clinical trial. Seventy young adults with moderate acne vulgaris received 2% metronidazole gel on the right side of their face and placebo on the left side of their face twice daily for 8 weeks. The number of inflamed and noninflamed facial lesions and side effects of treatment were documented on weeks 1, 2, 4, and 8. The patients’ overall satisfaction was recorded at the end of the study. For statistical analysis we used the repeated-measures analysis, the chi-square test, Fisher''s exact test, and the independent-samples t-test as appropriate.

Results:

Counts of inflamed and noninflamed facial lesions were comparable between the two sides at baseline. The number of the lesions was significantly lower on the metronidazole-treated side at all follow-up visits. Erythema and oily face decreased by 85.7% and 87.1%, respectively, on the metronidazole-treated side. Mild burning sensation and dryness on the metronidazole-treated side was reported by 3.4% and 22.9% of the patients, respectively. Eighty-eight percent of the patients were satisfied with the results of treatment on the metronidazole-treated side.

Conclusions:

Metronidazole gel (2%) is an effective, safe, and well-tolerated topical medication for moderate acne vulgaris.     

Radial pressure waves mediate apoptosis and functional angiogenesis during wound repair in ApoE deficient mice

This study aims to quantify by intravital microscopy and histological wound scoring the effect of radial pressure wave treatment (RPWT) on murine incisional wound healing. The dorsal skinfold chamber in mice was used for intravital microscopy, whereby an incisional wound was created within the chamber. RPWT to the wound was carried out using a ballistic pressure wave source (EMS Swiss DolorClast). Animals received a dose of 500 pulses at an energy flux rate of 0.1mJ/mm(2) and a frequency of 3Hz at day 1, 3, 5, 7, 9, and 11 post wounding. RPW treated and untreated ApoE depleted mice (ApoE(-/-)) were compared to normal healing wild type animals (WT). The microcirculation of the wound was analyzed quantitatively in vivo using epi-illumination intravital fluorescence microscopy. Tissue samples were examined ex vivo for wound scoring and immunohistochemistry. Upon RPWT total wound score in ApoE(-/-) mice was increased by 13% (not significant) on day 3, by 37% on day 7 (P<0.05), and by 39% on day 13 (P<0.05) when compared to untreated ApoE(-/-) mice. Improved wound healing was associated with an increase of functional angiogenetic density by 23% (not significant) on day 5, by 36% on day 7 (P<0.05), and by 41% on day 9 (P<0.05). Following RPWT, on day three we observed enhanced expression of capase-3 (2-fold), proliferating cell nuclear antibody (PCNA, 1,6-fold), and endothelial nitric oxide synthase (eNOS, 2.6-fold), all P<0.05. In conclusion repetitive RPWT accelerated wound healing in ApoE(-/-) mice by increasing functional neovascular density. In addition our findings strongly suggest that RPW may facilitate the linear progression of wound healing phases by fostering apoptosis.