Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the ...peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.
Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that
Valeton (Zingiberaceae) (
) extract was partly effective in ...decreasing prion aggregation and propagation in both in vitro and in vivo models.
extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrP
) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner.
extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrP
accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrP
accumulation in the spleen of mice was also reduced.
extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that
extract could contribute to investigating the modulation of prion propagation.
Background: We aimed to examine the impacts of digital healthy diet literacy (DDL) and healthy eating behaviors (HES) on fear of COVID-19, changes in mental health, and health-related quality of life ...(HRQoL) among front-line healthcare workers (HCWs). Methods: An online survey was conducted at 15 hospitals and health centers from 6–19 April 2020. Data of 2299 front-line HCWs were analyzed—including socio-demographics, symptoms like COVID-19, health literacy, eHealth literacy, DDL, HES, fear of COVID-19, changes in mental health, and HRQoL. Regression models were used to examine the associations. Results: HCWs with higher scores of DDL and HES had lower scores of FCoV-19S (regression coefficient, B, −0.04; 95% confidence interval, 95% CI, −0.07, −0.02; p = 0.001; and B, −0.10; 95% CI, −0.15, −0.06; p < 0.001); had a higher likelihood of stable or better mental health status (odds ratio, OR, 1.02; 95% CI, 1.00, 1.05; p = 0.029; and OR, 1.04; 95% CI, 1.00, 1.07; p = 0.043); and HRQoL (OR, 1.02; 95% CI, 1.01, 1.03; p = 0.006; and OR, 1.04; 95% CI, 1.02, 1.06; p = 0.001), respectively. Conclusions: DDL and HES were found as independent predictors of fear of COVID−19, changes in mental health status, and HRQoL in front-line HCWs. Improving DDL and HES should be considered as a strategic approach for hospitals and healthcare systems.
Many questions surround the underlying mechanism for the differential metabolic processing observed for the prion protein (PrP) in healthy and prion-infected mammals. Foremost, the physiological ...α-cleavage of PrP interrupts a region critical for both toxicity and conversion of cellular PrP (PrP
) into its misfolded pathogenic isoform (PrP
) by generating a glycosylphosphatidylinositol (GPI)-anchored C1 fragment. During prion diseases, alternative β-cleavage of PrP becomes prominent, producing a GPI-anchored C2 fragment with this particular region intact. It remains unexplored whether physical up-regulation of α-cleavage can inhibit disease progression. Furthermore, several pieces of evidence indicate that a disintegrin and metalloproteinase (ADAM) 10 and ADAM17 play a much smaller role in the α-cleavage of PrP
than originally believed, thus presenting the need to identify the primary protease(s) responsible. For this purpose, we characterized the ability of plasmin to perform PrP α-cleavage. Then, we conducted functional assays using protein misfolding cyclic amplification (PMCA) and prion-infected cell lines to clarify the role of plasmin-mediated α-cleavage during prion propagation. Here, we demonstrated an inhibitory role of plasmin for PrP
formation through PrP α-cleavage that increased C1 fragments resulting in reduced prion conversion compared with non-treated PMCA and cell cultures. The reduction of prion infectious titer in the bioassay of plasmin-treated PMCA material also supported the inhibitory role of plasmin on PrP
replication. Our results suggest that plasmin-mediated endoproteolytic cleavage of PrP may be an important event to prevent prion propagation.
•The cumulative live birth rate after ICSI was similar in couples with severe male factor infertility or normozoospermia.•The number of good-quality embryos did not differ significantly between ...severe male factor infertility and normozoospermic male.•Transfer of cleavage-stage embryo(s) was a significant (negative) predictor of cumulative live birth.
This study evaluated embryological and clinical outcomes in couples with severe male factor infertility versus those with normozoospermia undergoing ICSI and in vitro fertilisation.
This multicentre, retrospective cohort study included all couples who had undergone autologous ICSI cycles at My Duc Hospital and My Duc Phu Nhuan Hospital in Vietnam between January 2018 and January 2021 (female age < 35 years and males with severe male factor or normozoospermia based on the World Health Organization 2010 criteria). The primary outcome was the cumulative live birth rate after the first ICSI cycle.
A total of 1296 couples were included, including 648 with severe male factor infertility and 648 with normozoospermia. The number of two pronuclei zygotes, embryos, and frozen embryos was significantly lower in couples with severe male factor infertility compared with normozoospermia (p < 0.05). In contrast, there were no significant differences between the two groups with respect to cumulative pregnancy outcomes, including the live birth rate, and secondary outcomes including clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate.
Severe male factor infertility appeared to have an impact on the fertilisation and early developmental potential of embryos, but sperm quality did not affect cumulative clinical fertility outcomes.
Plasmin is a potent serin protease involved in a variety of biological functions, such as fibrinolysis and tissue remodeling. On performing an in vitro control assay to measure the activity of ...endogenous plasmin in cell lysates, a stimulatory effect of non-ionic detergent NP-40 on plasmin activity was discovered. Another non-ionic detergent, TX-100, also enhanced plasmin activity, while ionic detergents sodium deoxycholate and sodiem dodecyl sulfate abolished plasmin enzyme activity. Kinetic analysis of plasmin activity in the presence of NP-40 and TX-100 demonstrated an increase in Vmax; however, there was no change in Km values, suggesting that these detergents stimulate plasmin activity in a non-competitive manner. Fibrin plate assay indicates that NP-40 and TX-100 functionally stimulate plasmin activity by showing a dose-dependent increase in fibrinolysis.
•Plasmin activity is stimulated by nonionic detergents Nonidet P-40 and Triton X-100.•Nonidet P-40 and Triton X-100 facilitate plasmin enzyme kinetics in a non-competitive manner.•Nonidet P-40 and Triton X-100 increase fibrinolysis in fibrin plate assay by functionally stimulating plasmin activity.
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•Phosphorus (P) can be trapped inside silicaceous phytoliths.•In kinetic experiments we found a correlation between soluble silicon (Si) and P.•It suggests that P release might be ...controlled by the dissolution of phytolith.•Treatment temperature affects phytolith dissolution by changing removal rate of occluded carbon and modifying phytolith surface.•Pretreatment of the rice straw at 500–700°C is optimal to provide available P and Si.
Silicon (Si) is assimilated from soil by rice and is deposited in shoots in inter- and intracellularly, resulting in the formation of silicaceous structures, namely phytoliths. During the precipitation of Si, elements present in xylem/phloem sap, including phosphorus (P), can also be occluded in the phytolith. We examined the release of Si and P from the rice straw derived phytolith to elaborate the desilification mechanism, and the potential effects of phytolith as a nutrient ammendment. Data from batch heating experiments revealed that P trapped in the phytolith structure could be released accompanying with the dissolution of the phytolith. The highest values of soluble Si and P were found in the range of 500–700°C. The chemical composition, X-ray diffraction, infrared spectra and specific surface area (SSA) data suggested that the presence of occluded organic carbon at <500°C and crystallization of silica at >700°C were the main reasons for lower dissolution rates of phytolith and decreasing P release. With respect to practices of burning rice straw, it can be recommended that treatment temperature needs to be taken into account to maximize P release for crops.
Background The BRAF.sup.V600E gene encodes for the mutant BRAF.sup.V600E protein, which triggers downstream oncogenic signaling in thyroid cancer. Since most currently available methods have focused ...on detecting BRAF.sup.V600E mutations in tumor DNA, there is limited information about the level of BRAF.sup.V600E mRNA in primary tumors of thyroid cancer, and the diagnostic relevance of these RNA mutations is not known. Methods Sixty-two patients with thyroid cancer and non-malignant thyroid disease were included in the study. Armed with an ultrasensitive technique for mRNA-based mutation analysis based on a two step RT-qPCR method, we analysed the expression levels of the mutated BRAF.sup.V600E mRNA in formalin-fixed paraffin-embedded samples of thyroid tissues. Sanger sequencing for detection of BRAF.sup.V600E DNA was performed in parallel for comparison and normalization of BRAF.sup.V600E mRNA expression levels. Results The mRNA-based mutation detection assay enables detection of the BRAF.sup.V600E mRNA transcripts in a 10,000-fold excess of wildtype BRAF counterparts. While BRAF.sup.V600E mutations could be detected by Sanger sequencing in 13 out of 32 malignant thyroid cancer FFPE tissue samples, the mRNA-based assay detected mutations in additionally 5 cases, improving the detection rate from 40.6 to 56.3%. Furthermore, we observed a surprisingly large, 3-log variability, in the expression level of the BRAF.sup.V600E mRNA in FFPE samples of thyroid cancer tissue. Conclusions The expression levels of BRAF.sup.V600E mRNA was characterized in the primary tumors of thyroid cancer using an ultrasensitive mRNA-based mutation assay. Our data inspires further studies on the prognostic and diagnostic relevance of the BRAF.sup.V600E mRNA levels as a molecular biomarker for the diagnosis and monitoring of various genetic and malignant diseases. Keywords: Thyroid cancer, BRAF mutation, mRNA mutation assay, Diagnosis
Colloid-sized microplastics (MPs) are ubiquitous in aquatic environments and can share the same transport route together with various crystalline, poorly crystalline and freshly formed iron oxides. ...However, the colloidal interactions between these colloid constituents are not fully understood. This study was designed to investigate the colloidal properties of polystyrene microplastics (PSMPs) under the influence of haematite, goethite, ferrihydrite and freshly formed Fe oxide (FFFO). Dynamic light scattering was coupled with a test tube method to observe changes in the surface charge and colloidal dynamics of suspensions of PSMPs and Fe oxides. The overall effects on the aggregation of PSMPs are found to decrease in the following order: FFFO > ferrihydrite > goethite > haematite. The effects of these Fe oxides are found to strongly depend on pH. While the crystalline oxides play a dominant role in the acidic environment, poorly crystalline oxides show greater effects on PSMP aggregation in an alkaline environment. Heteroaggregation due to decreasing electrostatic interactions is the major mechanism that governs the colloidal dynamics of PSMPs and Fe oxides. It can be inferred that the copresence of Fe oxides and MPs can delay the transport of MPs or even change the destination for MPs.
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•PSMPs carry negative charges and exhibit high mobility in aqueous solution.•Fe oxides show their ability to stimulate aggregation of PSMPs.•Heteroaggregation due to electrostatic interactions is the major mechanism.•Fe oxides and PSMPs can delay the transport of PSMPs.
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