On the surface and beyond. Degradation morphologies affecting plant ash‐based archaeological glass from Kafir Kala (Samarkand, Uzbekistan)

The study focuses on an assemblage of glass finds from the citadel of Kafir Kala, Uzbekistan, located along one of the major Eurasian branches of the “Silk Roads” with a consistent occupation between the 8th and 12th century CE. Glass fragments for this study were selected based on marked surface alterations they showed, with stratified deposits of different thickness and colours. Starting from a preliminary observation under Optical Microscope, fragments were clustered into four main groups based on the surface appearance of the alterations; Scanning Electron Microscopy investigations of the stratigraphy of the alteration products were then carried out, to evaluate micro‐textural, morphological and compositional features. Data from the analyses allowed identifying preferential patterns of development of the various degradation morphologies, linkable to compositional alterations of the glass due to burial environment and the alkali leaching action of the water. Iridescence, opaque weathering (at times associated with black stains), and blackening were identified as recurring degradation morphologies; as all but one sample were made of plant ash‐based glass, results show no specific correlation between glass composition and the occurrence of one or the other degradation pattern, often found together. Framed in a broad scenario, the paper aims to set the basis for the development of a study approach dedicated to the degradation morphologies affecting archaeological glasses, a topic still lacking systematisation and in‐depth dedicated literature

Antihyperlipidemic Activity of Terminalia Chebula Retz Extract-Loaded Phytosomes: Development and Characterization

Ethnopharmacological evidence has demonstrated that Terminalia chebula Retz is traditionally employed for the management of hepatic ailments. Presently, a significant number of prevalent diseases and nutritional disorders are managed through the utilization of natural remedies. The efficacy of herbal medications relies on the administration of a sufficient dosage of the therapeutically active component. However, there is a significant constraint in terms of their bioavailability when taken via oral or topical routes. Phytosomes are a novel class of herbal formulations that have been recently introduced. These formulations exhibit enhanced absorption properties, leading to improved bioavailability and efficacy compared to traditional phyto compounds or botanical extracts. The objective of the current investigation was to assess the qualitative and quantitative phytochemical analysis, high-performance liquid chromatography, optical microscopic research, and in vitro antioxidant properties of Terminalia chebula Retz leaves obtained from the Bhopal region of Madhya Pradesh. The hydroalcoholic extract of phytosome was prepared using a mixture of phospholipids and cholesterol. The characterization of phytosome was conducted using various analytical techniques, including Fourier-transform infrared spectroscopy, determination of entrapment efficiency, measurement of particle size and size distribution, examination under an optical microscope, high-performance liquid chromatography analysis. The concurrent utilization of phospholipids and Terminalia chebula Retz has the potential to produce a synergistic outcome. This synergistic effect can be assessed by evaluating the free radical scavenging activity using the DPPH model

Enhancing the analytical performance of laser-induced breakdown spectroscopy

This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The objective of this work is to enhance the analytical capabilities of laser-induced breakdown spectroscopy (LIBS). LIBS is a method of elemental analysis in which powerful laser pulses are focused on a sample to form a microplasma. LIBS is perhaps the most versatile elemental analysis method, applicable to a variety of different real-world analysis problems. Therefore, it is important to enhance the capabilities of the method as much as possible. Accomplishments include: (1) demonstration of signal enhancements of 5--30 times from soils and metals using a double pulse method; (2) development of a model of the observed enhancement obtained using double pulses; (3) demonstration that the analytical performance achievable using low laser-pulse energies (10 and 25 mJ) can match that achievable using an energy of 100 mJ; and (4) demonstration that time-gated detection is not necessary with LIBS

In search for potential antidiabetic compounds from natural sources: docking, synthesis and biological screening of small molecules from Lycium spp. (Goji)

© 2019 Current clinical antidiabetic drugs, like rosiglitazone 1, have been implicated in some serious side effects like edema, weight gain, and heart failure, making it necessary to find alternative agents. Partial agonists of peroxisome-proliferator activated receptor-gamma (PPARγ) were determined to possess improved insulin sensitivity without undeseirable side-effects when compared to full agonists of PPARγ, like rosiglitazone 1. The traditional Chinese medicine (TCM) plants, Goji (Lycium barbarum and Lycium chinense) are widely used for treating symptoms related to various diseases including diabetes and hypertension. Twenty-seven reported compounds from Goji were docked into both partial- and full-agonist binding sites of PPARγ. Amongst the docked compounds, phenylethylamide-based phytochemicals (5–9) (termed as tyramine-derivatives, TDs) were found to possess good docking scores and binding poses with favorable interactions. Synthesis of 24 TDs, including three naturally occuring amides (6, 8, 9) were synthesized and tested for PPARγ gene induction with cell-based assay. Three compounds showed similar or higher fold induction than the positive control, rosiglitazone. Among these three active TDs, trans-N-feruloyloctopamine (9) and tyramine derivatives-enriched extract (TEE) (21%) of the root bark of L. chinense were further studied in vivo using db/db mice. However, both TEE as well as 9 did not show significant antidiabetic properties in db/db mice. In vivo results suggest that the proposed antidiabetic property of Lycium species may not be due to tyramine derivatives alone. Further studies of tyramine derivatives or enriched extract(s) for other bioactivities like hypocholesterolemic activities, and studies of novel isolated compounds from Goji will enable a more complete understanding of their bioactivities

Investigating the Effects of Homocysteine as an Agonist on Invertebrate Glutamatergic Synapses

Hyperhomocysteinemia (HHcy) in mammals can produce neurological deficits, such as memory loss. The cause of the neurological issues is assumed to be due to homocysteine (HCY) binding to glutamatergic receptors in the central nervous system (CNS). High levels of HCY in the CNS are also associated with Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease. Thus, understanding the detailed mechanisms of HCY in model preparations could be useful in developing potential treatments to neurodegenerative diseases with overlapping symptoms to HHcy. The aim of this study is to investigate the efficacy of HCY as an agonist at glutamatergic synapses in invertebrates. The glutamatergic synapses of the larval Drosophila melanogaster (D. melanogaster) and Procambarus clarkii (P. clarkii) neuromuscular junctions (NMJs) were utilized to examine the effects of applying HCY. Measurements of evoked synaptic transmission in both preparations revealed that 100 mM of HCY did not have any consistent effect. The expectation was that the acute action of HCY would have activated the glutamate receptors and then desensitized them so evoked transmission would be blocked. The pharmacological receptor profile of these NMJ receptors are of a quisqualate subtype and not a kainate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate receptor (NMDA) subtype. Consequently, HCY may not have any action on quisqualate glutamate receptor subtypes. The findings of this experiments could provide clinical implications regarding relevant pharmacological treatments in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease

Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

<p>Abstract</p> <p>Background</p> <p>Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2). The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade.</p> <p>Methods</p> <p>Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV) was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF₂α production. Proliferation assays were also performed in presence of different prostaglandins (PGs).</p> <p>Results</p> <p>Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor <it>in vivo </it>in skeletal muscle cells and in satellite cells and <it>in vitro </it>in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-^12,14-prostaglandin J₂(15Δ-PGJ₂), a product of COX-2-derived prostaglandin D₂, stimulated myoblast proliferation, but not PGE₂and PGF₂α.</p> <p>Conclusions</p> <p>Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.</p

CXCR4 Expression in Prostate Cancer Progenitor Cells

Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44+/CD133+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy