Functional expression and impact of testis-specific gene antigen 10 in breast cancer: a combined in vitro and in silico analysis

Introduction: Testis-specific gene antigen 10 (TSGA10) is a less-known gene, which is involved in the vague biological paths of different cancers. Here, we investigated the TSGA10 expression using different concentrations of glucose under hypoxia and also its interaction with the hypoxia-inducible factor 1 (HIF-1). Methods: The breast cancer MDA-MB-231 and MCF-7 cells were cultured with different concentrations of glucose (5.5, 11.0 and 25.0 mM) under normoxia/hypoxia for 24, 48, and 72 hours and examined for the HIF-1α expression and cell migration by Western blotting and scratch assays. The qPCR was employed to analyze the expression of TSGA10. Three-dimensional (3D) structure and the energy minimization of the interacting domain of TSGA10 were performed by MODELLER v9.17 and Swiss-PDB viewer v4.1.0/UCSF Chimera v1.11. The UCSF Chimera v1.13.1 and Hex 6.0 were used for the molecular docking simulation. The Cytoscape v3.7.1 and STRING v11.0 were used for protein-protein interaction (PPI) network analysis. The HIF-1a related hypoxia pathways were obtained from BioModels database and reconstructed in CellDesigner v4.4.2. Results: The increased expression of TSGA10 was found to be significantly associated with the reduced metastasis in the MDA-MB-231 cells, while an inverse relationship was seen between the TSGA10 mRNA level and cellular migration but not in the MCF-7 cells. The C-terminal domain of TSGA10 interacted with HIF-1α with high affinity, resulting in PPI network with 10 key nodes (HIF-1α, VEGFA, HSP90AA1, AKT1, ARNT, TP53, TSGA10, VHL, JUN, and EGFR). Conclusions: Collectively, TSGA10 functional expression alters under the hyper-/hypo-glycemia and hypoxia, which indicates its importance as a candidate bio-target for the cancer therapy

Anticancer potential of Thevetia peruviana fruit methanolic extract

Abstract Background: Thevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. Methods: The cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry. Results: The T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 μg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides. Conclusion: T. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines. Keywords: Cytotoxic activity, Anti-proliferative activity, Motility, Apoptosis, Human cancer cells, Flavonoid, Cardiac glycoside

Hyers-Ulam-Rassias Stability of Derivations in Proper JCQ*-triples

In this paper, we investigate stability of derivations in proper JCQ*-triples associated to the following Pexiderized functional equation f(x + y + z) = f(0)(x) + f(1)(y) + f(2)(z)

A new strategy for the synthesis of modified novolac resin and its polymer/clay nanocomposite

A novel epoxy nanocomposite composed of epoxidized novolac (ENR), epoxidized polystyrene (EPSt), and nanoclay was fabricated and characterized successfully. For this purpose, the novolac was epoxylated using a substitution nucleophilic reaction between hydroxyl group of novolac and chlorine group of epichlorohydrin. The EPSt was synthesized through the oxidizing of an allylated PSt (All-PSt). A mixture of ENR (70 wt%), EPSt (20 wt%) and Cloisite®R 20A (5 wt%) was cured using ethylenediamine (EDA; 5 wt%) to afford a C-ENR-EPSt/clay nanocomposite. The transition electron microscopy (TEM) as well as powder X-ray diffraction (XRD) analysis revealed that the fabricated nanocomposite has an exfoliated structure. As the thermal property studies results, the addition of EPSt as well as Cloisite® 20A has synergistic effect on the thermal stability of the ENR resin

Assessment of <i>MC1R</i> and <i>&#945;</i><i>-MSH</i> gene sequences in Iranian vitiligo patients

Background: Vitiligo is an acquired pigmentary disorder of the skin that is caused by unknown factors and is characterized by white and depigmented patches that enlarge and become more numerous with time. Genetic factors, oxidative stress, autoimmunity, and neurochemical agents, such as catecholamines might also contribute to vitiligo. Cutaneous pigmentation is determined by the amounts of eumelanin and pheomelanin synthesized by the epidermal melanocytes and interference of melanocortin-1 receptor (MC1R), a G-protein coupled receptor, its normal agonist, alpha-melanocyte stimulating hormone (&#945;-MSH), and key enzymes, such as tyrosinase, to protect against sun-induced DNA damage. The MC1R, a 7 pass trans-membrane G-protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to pheomelanin production, resulting in a red or yellow coat color. Aim: In this research, we aim to examine the genetic variety of MC1R and &#945;-MSH gene in 20 Iranian vitiligo patients and 20 healthy controls. Materials and Methods: Analysis of the MC1R coding gene was performed with direct sequencing. Results: We found the following 9 MC1R coding region variants: Arg163Gl (G488A), Arg227Leu (G680A), Val 97Phe (G289T), Asp184Asn (G550A), Arg227Lys (G680A), Arg142His (G425A), Val60Leu (G178T), Val247Met (C739A), and Val174Ile (G520A). We also found 2 frameshift changes: one of them was the Insertion of C (frameshift in Pro136, stop at Trp148) and the other, Insertion of G (frameshift in Pro256, stop at Trp 333). Of all the changes, the most common was Val60Leu at 5&#x0025; in patients vs 20&#x0025; in controls, Val247Met at 15&#x0025; in patients vs 0&#x0025; in controls and Val174Ile at 15&#x0025; in controls and 0&#x0025; in patients. The other variants showed a frequency &lt;5&#x0025; in both patients and controls. Also in this study, we have examined the frequency of single nucleotide polymorphisms within the &#945;-MSH genes with direct sequencing in 20 patients and 20 healthy subjects but found no changes along this gene. Conclusion: We could not find any relationship between MC1R and &#945;-MSH genes and their effect on the disease in Iranian vitiligo patients

Essential oils of hedgenettles (Stachys inflata, S. lavandulifolia, and S. byzantina) have antioxidant, anti-Alzheimer, antidiabetic, and anti-obesity potential: A comparative study

Stachys species (hedgenettle or woundwort) are important medicinal plants known for their flavor and fragrance. They are widely consumed in Europe and Asia as aromatic herbal teas. In this work, essential oils (EOs) of three popular Stachys herbs namely Stachys inflata Benth., S. lavandulifolia Vahl., and S. byzantina K. Koch were in- vestigated for their chemical composition, antioxidant activity, and health benefits. The major volatile com- ponents of S. inflata were identified as germacrene D (21.6 %) and β-pinene (15.6 %). S. lavandulifolia contained mainly germacrene D (22.5 %) and α-pinene (15.5 %) whereas S. byzantina showed hexahydrofarnesyl acetone (25.7 %) and valeranone (17.1 %) as major volatile constituents. EOs exhibited promising reducing power in cupric reducing antioxidant capacity (58−204 mg Trolox equivalents/g EO) and ferric reducing antioxidant power (32−104 mg Trolox equivalents/g EO) assays. Moreover, the metal chelating activity of EOs was de- termined from 15 to 36 mg EDTA equivalents/g EO. S. inflata showed anti-Alzheimer’s disease effect through inhibition of cholinesterase enzymes (5.2–7.8 mg galantamine equivalents/g EO). All samples had a strong antidiabetic effect (α-glucosidase inhibition) with values ranging from 4.47 to 4.62 mmol acarbose equivalents/g EO. Also, remarkable anti-obesity (lipase inhibition with 88−159 mg orlistat equivalents/g EO) and anti-hy- perpigmentation (tyrosinase inhibition with 24−35 mg kojic acid equivalents/g EO) potential were observed for Stachys EOs. These findings showed that EOs of hedgenettle (betony) plants could be employed in the pre- paration of formulations to be used in cosmetics, food, and pharmaceutical products due to their valuable an- tioxidant, neuroprotective, hypoglycemic, anti-obesity, and skin-care effects

On Harmonious Colouring of Trees

Let G be a simple graph and (G) denote the maximum degree of G. A harmonious colouring of G is a proper vertex colouring such that each pair of colours appears together on at most one edge. The harmonious chromatic number h(G) is the least number of colours in such a colouring. In this paper it is shown that n if T is a tree of order n and (T) , then there exists a harmonious colour-2 ing of T with (T) + 1 colours such that every colour is used at most twice. Thus h(T) = (T)+1. Moreover, we prove that if T is a tree of order n and (T) d n 2 e, then there exists a harmonious colouring of T with d n e + 1 colours such that every 2 colour is used at most twice. Thus h(T) d n e + 1.