Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1–4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1–4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.
Malignant gliomas are associated with extremely poor clinical outcomes in both humans and dogs, and novel therapies are needed. Glioma-bearing canine patients may serve as promising preclinical models for human therapies, including complementary medicine. The objective of this study was to evaluate the effects of mistletoe extract (Viscum album) alone and in combination with mebendazole in an in vitro model of canine high-grade astrocytoma using the cell line SDT-3G. SDT-3G cells were exposed to a range of concentrations of mistletoe extract alone to obtain an IC50. In separate experiments, cells were exposed to mebendazole at a previously determined IC50 (0.03 µM) alone or in conjunction with varying concentrations of mistletoe extract to determine the additive effects. The IC50 for mistletoe alone was 5.644 ± 0.09 SD μg/mL. The addition of mistletoe at 5 μg/mL to mebendazole at 0.03 µM led to increased cell death compared to what would be expected for each drug separately. The cytotoxicity of mistletoe in vitro and its additive effect with mebendazole support future expanded in vitro and in vivo studies in dogs and supply early evidence that this may be a useful adjunct therapeutic agent for use in glioma-bearing dogs. To the authors’ knowledge, this is the first published report of Viscum album extract in canine glioma.
The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition.
We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD.
We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, −omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD.
Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.
Nanofibers have emerged as a potential novel platform due to their physicochemical properties for healthcare applications. Nanofibers’ advantages rely on their high specific surface-area-to-volume and highly porous mesh. Their peculiar assembly allows cell accommodation, nutrient infiltration, gas exchange, waste excretion, high drug release rate, and stable structure. This review provided comprehensive information on the design and development of natural-based polymer nanofibers with the incorporation of herbal medicines for the treatment of common diseases and their in vivo studies. Natural and synthetic polymers have been widely used for the fabrication of nanofibers capable of mimicking extracellular matrix structure. Among them, natural polymers are preferred because of their biocompatibility, biodegradability, and similarity with extracellular matrix proteins. Herbal bioactive compounds from natural extracts have raised special interest due to their prominent beneficial properties in healthcare. Nanofiber properties allow these systems to serve as bioactive compound carriers to generate functional matrices with antimicrobial, anti-inflammatory, antioxidant, antiseptic, anti-viral, and other properties which have been studied in vitro and in vivo, mostly to prove their wound healing capacity and anti-inflammation properties.
The role of aldosterone in regulating K+ excretion in the distal nephron is well established in kidney physiology. In addition to effects on the kidney, aldosterone modulates K+ and Na+ transport in salivary fluid, sweat, airway epithelia, and colonic fluid. More controversial and less well defined is the role of aldosterone in determining the internal distribution of K+ across cell membranes in non-transporting epithelia. In vivo studies have been limited by the difficulty in accurately measuring overall K+ balance and factoring in both variability and secondary changes in acid-base balance, systemic hemodynamics, and other K+-regulatory factors such as hormones and adrenergic activity. Despite these limitations, the aggregate data support a contributory role of aldosterone along with insulin and catecholamines in the normal physiologic regulation of internal K+ distribution. The authors speculate differences in tissue sensitivity to aldosterone may also contribute to differential tissue response of cardiac and skeletal muscle to conditions of total body K+ depletion.
Keratin is among the most abundant structural proteins of animal origin, however it remains broadly underutilized.
Bioinformatic investigation was performed to evaluate selected keratins originating from mass-produced waste products, i.e., chicken feathers and pig hair, as potential sources of bioactive peptides.
Pepsin, trypsin, chymotrypsin, papain, and subtilisin were used for in silico keratinolysis with the use of “Enzyme(s) action” and fragmentomic analysis of theoretical products was performed using “Profiles of potential biological activity” in BIOPEP-UWM database of bioactive peptides. Bioactivity probability calculation and toxicity prediction of the peptides obtained were estimated using PeptideRanker and ToxinPred tools, respectively.
Our results showed that the keratins are a potential source of a variety of biopeptides, including dipeptidyl peptidase IV, angiotensin converting enzyme, prolyl endopeptidase inhibitory and antioxidative. Papain and subtilisin were found to be the most appropriate enzymes for keratin hydrolysis. This study presents possible structures of keratin-derived bioactive peptides that have not been previously described.
Our data suggest additional in vitro and in vivo studies to verify theoretical predictions and further investigate the possibility of using keratin-rich waste as a source of peptide nutraceuticals.
Natural products have antitumor, anti-inflammatory, antioxidant, and other pharmacological activities and are an important source of drugs for prevention and treatment of various diseases. However, the inherent defects of natural products in physiological media such as poor solubility and stability and short biological half-life limit their clinical application. In recent years, more and more attention has been paid to the science of drug delivery by nanoscale materials. A large number of in vitro and in vivo studies have further confirmed the efficacy and safety of nanomedicine based on natural products in preclinical models of various diseases. In this review, we summarized the achievements of nanomaterials in improving the efficacy of natural products, introduced the research progress in several key fields of natural product-based nanomedicine in medical application, and discussed the challenges and prospects of clinical transformation of nanomedicine.