Cross-Omics Analysis of Fenugreek Supplementation Reveals Beneficial Effects Are Caused by Gut Microbiome Changes Not Mammalian Host Physiology

Herbal remedies are increasing in popularity as treatments for metabolic conditions such as obesity and Type 2 Diabetes. One potential therapeutic option is fenugreek seeds (Trigonella foenum-graecum), which have been used for treating high cholesterol and Type 2 diabetes. A proposed mechanism for these benefits is through alterations in the microbiome, which impact mammalian host metabolic function. This study used untargeted metabolomics to investigate the fenugreek-induced alterations in the intestinal, liver, and serum profiles of mice fed either a 60% high-fat or low-fat control diet each with or without fenugreek supplementation (2% w/w) for 14 weeks. Metagenomic analyses of intestinal contents found significant alterations in the relative composition of the gut microbiome resulting from fenugreek supplementation. Specifically, Verrucomicrobia, a phylum containing beneficial bacteria which are correlated with health benefits, increased in relative abundance with fenugreek. Metabolomics partial least squares discriminant analysis revealed substantial fenugreek-induced changes in the large intestines. However, it was observed that while the magnitude of changes was less, significant modifications were present in the liver tissues resulting from fenugreek supplementation. Further analyses revealed metabolic processes affected by fenugreek and showed broad ranging impacts in multiple pathways, including carnitine biosynthesis, cholesterol and bile acid metabolism, and arginine biosynthesis. These pathways may play important roles in the beneficial effects of fenugreek.     

An Overview,Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon-Like Peptide-1 Receptor

Due to uncomfortable injection regimens of peptidic agonists of glucagon-like peptide-1 receptor (GLP-1R), orally available nonpeptide positive allosteric modulators (PAMs) of GLP-1Rs are foreseen as the possible future mainstream therapy for type 2 diabetes. Herein, current GLP-1R PAMs are reviewed. Based on the effectiveness and in silico predicted physicochemical properties, pharmacokinetics, and toxicity, possible candidates for further development as oral drugs were selected. The suggestion is that GLP-1R PAMs might be used orally alone or in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors, which could offer an optimal treatment option next to metformin monotherapy in type 2 diabetes mellitus, or in a wider spectrum of indications. Quercetin acts as a GLP-1R PAM and DPP-4 inhibitor, and therefore, might be considered as a pioneering agent with a dual mechanism of action, in terms of GLP-1R positive allosteric modulation and DPP-4 inhibition for potentiating GLP-1 dependent effects.     

Poly(ethylene glycol)-interpenetrated genipin-crosslinked chitosan hydrogels: Structure,pH responsiveness,gelation kinetics,and rheology

In the development of pH-responsive chitosan-based hydrogels, achieving reproducible porosity and swelling behavior is essential for the design of hydrogel networks. Herein, we enhance the level of control in hydrogel microarchitecture by incorporating poly(ethylene glycol) (PEG) into the chitosan–genipin matrix. Hydrogels, varied in composition, were synthesized under mild conditions (37°C, 1 atm, 24 hr), yielding microporous structures with a pore diameter ranging from 11 to 57 μm and an average cross-sectional porosity of approximately 40–64%. Compared to chitosan–genipin hydrogels without PEG, presence of PEG in concentrations up to 1.9 mM generated the same effect as would increase in genipin content, yielding structures with a smaller pore diameter, a lower swelling degree in pH 2 buffer and a higher elastic modulus. Considering cost effectiveness and scale-up, reducing genipin content by the addition of PEG is favorable. Importantly, hydrogel samples containing higher concentrations of PEG (2.9 mM and above) showed a sudden increase in the swelling degree accompanied with a decrease in the elastic modulus. Findings showcase the potential variation in the composition of these hydrogels has in yielding scaffolds with significantly different physico-chemical behaviors.     

Defining a strain‐induced time constant for oriented low shear‐induced structuring in high consistency MFC/NFC‐filler composite suspensions

Micro and nanofibrillated cellulose is an essentially one‐dimensional high aspect‐ratio particle material, which can undergo two‐dimensional layer (band) structuring under shear. Controlling the evolving rheological properties in aqueous suspension is essential for industrial applications in composite materials. This study focuses on an as yet considered to be unreported phenomenon of structure hardening under low shear. The timescale of the quasi gelation‐controlled structure formation under low shear is studied using the large gap vane‐in‐cup geometry of the Brookfield viscometer. It is proposed that localized structure forms within continuous shear bands, similar to quasi liquid‐crystal formation. By extrapolating a characteristic structure growth parameter to the rotation speed at which it becomes zero, the strain‐induced structure time constant, t_gel, can be obtained as (= f (Ω)) = 1/t_gel for the range Ω = 10–100/min. The time constant of low shear structure formation is shown to be separable from the static viscoelastic structure build under oscillation in concentrated composite suspension using plate‐plate geometry, which is manifest by a Weissenberg normal force response on switching to applied shear, when the time constant of structuration t_gel is long. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42827.     

Electrochemical routes for environmentally friendly recycling of rare-earth-based (Sm–Co) permanent magnets

Journal of Applied Electrochemistry - The consumption of critical raw materials, especially those in permanent magnets of Nd–Fe–B and Sm–Co-type, has significantly grown in the...     

Evaluation of a Novel Plasmid for Simultaneous Gene Electrotransfer-Mediated Silencing of CD105 and CD146 in Combination with Irradiation

Targeting tumor vasculature through specific endothelial cell markers represents a promising approach for cancer treatment. Here our aim was to construct an antibiotic resistance gene-free plasmid encoding shRNAs to simultaneously target two endothelial cell markers, CD105 and CD146, and to test its functionality and therapeutic potential in vitro when delivered by gene electrotransfer (GET) and combined with irradiation (IR). Functionality of the plasmid was evaluated by determining the silencing of the targeted genes using qRT-PCR. Antiproliferative and antiangiogenic effects were determined by the cytotoxicity assay tube formation assay and wound healing assay in murine endothelial cells 2H-11. The functionality of the plasmid construct was also evaluated in malignant melanoma tumor cell line B16F10. Additionally, potential activation of immune response was measured by induction of DNA sensor STING and proinflammatory cytokines by qRT-PCR in endothelial cells 2H-11. We demonstrated that the plasmid construction was successful and can efficiently silence the expression of the two targeted genes. As a consequence of silencing, reduced migration rate and angiogenic potential was confirmed in 2H-11 endothelial cells. Furthermore, induction of DNA sensor STING and proinflammatory cytokines were determined, which could add to the therapeutic effectiveness when used in vivo. To conclude, we successfully constructed a novel plasmid DNA with two shRNAs, which holds a great promise for further in vivo testing.     

Characteristics of Retinitis Pigmentosa Associated with ADGRV1 and Comparison with USH2A in Patients from a Multicentric Usher Syndrome Study Treatrush

In contrast to USH2A, variants in ADGRV1 are a minor cause of Usher syndrome type 2, and the associated phenotype is less known. The purpose of the study was to characterize the retinal phenotype of 18 ADGRV1 patients (9 male, 9 female; median age 52 years) and compare it with that of 204 USH2A patients (111 male, 93 female; median age 43 years) in terms of nyctalopia onset, best corrected visual acuity (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) features. There was no statistical difference in the median age at onset (30 and 18 years; Mann–Whitney U test, p = 0.13); the mean age when 50% of the patients reached legal blindness (≥1.0 log MAR) based on visual acuity (64 years for both groups; log-rank, p = 0.3); the risk of developing advanced retinal degeneration (patch or atrophy) with age (multiple logistic regression, p = 0.8); or the frequency of cystoid macular edema (31% vs. 26%, Fisher’s exact test, p = 0.4). ADGRV1 and USH2A retinopathy were indistinguishable in all major functional and structural characteristics, suggesting that the loss of function of the corresponding proteins produces similar effects in the retina. The results are important for counseling ADGRV1 patients, who represent the minor patient subgroup.     

Targeting Mitochondria in Diabetes

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.     

A comparative study of direct and indirect evaluation of piezoelectric properties of electrophoreticaly deposited (Ba,Ca) (Zr,Ti)O3 lead-free piezoceramics

The development and optimisation of piezoceramics are targeted usually to enhance their piezoelectric properties evaluated by both the direct or indirect measurement methods. The presented work aims to elaborate on the correlation of one direct (Berlincourt) and two indirect (convert and field-dependent) piezoelectric measurement methods on various material states. The role of the ceramic powder treatment by ball milling and electrophoretic deposition (EPD) technique on the determined electric properties as well as basic physical and mechanical properties of (Ba_0.85Ca_0.15) (Zr_0.1Ti_0.9)O₃ ceramics (BCZT) was investigated. It was found that the EPD technologically supported by milling allows obtaining thick and dense deposits (>2 mm). After sintering, the BCZT ceramics with a relative density of >95%, hardness in the range of 2.3–2.9 GPa and piezoelectric coefficients of d₃₃* = 940 pm/V, d_33(E=0) = 427 pm/V and d₃₃ = 364 pC/N can be achieved. Reported results also suggest that indirect (field-dependent) and direct (Berlincourt) measurements of the piezoelectric coefficients can be comparable at optimal poling conditions.     

Hydrogenation properties of Hf-Ni intermetallics - Experimental and theoretical investigation

The hydrogenation properties of HfNi and Hf₂Ni₇ intermetallics were investigated at the constant pressure of 1 bar and in the temperature ranges 373-573 K for HfNi and 323-473 K for Hf₂Ni₇. The kinetic parameters, rate constants and activation energies of the absorption processes were determined. Maximal hydrogen absorption, i.e., number of hydrogen atoms absorbed per metal atom, H/M, are 1.05 and 0.04 achieved at 373 K for HfNi and Hf₂Ni₇, respectively. Multiple hydriding/dehydriding was found to influence the improvement of the kinetic parameters. XRD and SEM methods were used to investigate the structural and morphological changes of the samples due to hydrogen absorption. The thermodynamic parameters of hydriding together with the structural properties of the intermetallics and their hydrides, calculated using the full-potential linearized augmented plane waves (FP-LAPW) code based on the density functional theory (DFT), were utilized for the sake of explaining the experimental investigations.