Nature-derived compounds modulating Wnt/β-catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases

Abstract The Wnt/β-catenin signaling is a conserved pathway that has a crucial role in embryonic and adult life. Dysregulation of the Wnt/β-catenin pathway has been associated with diseases including cancer, and components of the signaling have been proposed as innovative therapeutic targets, mainly for cancer therapy. The attention of the worldwide researchers paid to this issue is increasing, also in view of the therapeutic potential of these agents in diseases, such as Parkinson's disease (PD), for which no cure is existing today. Much evidence indicates that abnormal Wnt/β-catenin signaling is involved in tumor immunology and the targeting of Wnt/β-catenin pathway has been also proposed as an attractive strategy to potentiate cancer immunotherapy. During the last decade, several products, including naturally occurring dietary agents as well as a wide variety of products from plant sources, including curcunim, quercetin, berberin, and ginsenosides, have been identified as potent modulators of the Wnt/β-catenin signaling and have gained interest as promising candidates for the development of chemopreventive or therapeutic drugs for cancer. In this review we make an overview of the nature-derived compounds reported to have antitumor activity by modulating the Wnt/β-catenin signaling, also focusing on extraction methods, chemical features, and bio-activity assays used for the screening of these compounds

Collagen Fiber Arrangement in Temporo-Mandibular Joint (TMJ) Disks from Human Subjects with Functional Diseases. Scanning Electron Microscopy Investigations

Twelve articular disks from patients with temporo-mandibular joint (TMJ) arthropathy were studied and compared with two normal disks. Scanning electron microscopy (SEM) examination of the surfaces and of longitudinal and cross-sections of the disks allowed the observation of the arrangement of the collagen fiber component in different parts of the disk. The superficial part of the articular disks appears to be formed by rather compact fibers. The internal portion is usually formed by bundles of collagen fibers in sheets, alternating with isolated fibers arranged in a parallel or irregular way. In some samples, blood vessels were observed. Our investigations suggested that the appearance of vascularization is the first remarkable histological change that can be observed in functionally abnormal articular disks

Endoarticular Loose Bodies and Calcifications of the Disk of the Temporomandibular Joint: Morphological Features and Chemical Composition

We studied articular disks and endoarticular loose bodies taken from patients suffering from different types of temporomandibular joint (TMJ) pathology. The scanning electron microscopy (SEM) analysis of the disks and the endoarticular loose bodies was followed by a chemical-compositional analysis using an energy dispersive spectrometer (EDS) and by characterization of the crystalline phases by X-ray powder diffraction (XRD). The articular disks were composed of a central radio-opaque area lacking any evident structural features, surrounded by compact bundles of collagen fibers. EDS and XRD analyses showed that endodiscal radio-opaque areas were hydroxyapatite. By SEM, we observed a fibrous network only in circumscribed areas of the endoarticular loose bodies. The chemical-compositional analysis showed that the loose bodies were composed of calcite (CaCO3). The results of this investigation, along with the clinical history of the patients, allow us to formulate some hypotheses regarding the etiopathogenesis of these structural anomalies. The endodiscal calcifications could be the result of a chronic inflammatory process that produces displastic alterations of the articular disk. Moreover, an acute inflammatory process with modifications in the mechanisms of the synovial fluid turnover seems to be the event that leads to the formation of endoarticular loose bodies

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Antimicrobial and toxicological activities of five medicinal plant species from Cameroon Traditional Medicine

<p>Abstract</p> <p>Background</p> <p>Infectious diseases caused by multiresistant microbial strains are on the increase. Fighting these diseases with natural products may be more efficacious. The aim of this study was to investigate the <it>in vitro </it>antimicrobial activity of methanolic, ethylacetate (EtOAc) and hexanic fractions of five Cameroonian medicinal plants (<it>Piptadeniastum africana</it>, <it>Cissus aralioides, Hileria latifolia, Phyllanthus muellerianus </it>and <it>Gladiolus gregasius) </it>against 10 pathogenic microorganisms of the urogenital and gastrointestinal tracts.</p> <p>Methods</p> <p>The fractions were screened for their chemical composition and <it>in vivo </it>acute toxicity was carried out on the most active extracts in order to assess their inhibitory selectivity.</p> <p>The agar well-diffusion and the micro dilution methods were used for the determination of the inhibition diameters (ID) and Minimum inhibitory concentrations (MIC) respectively on 8 bacterial species including two Gram positive species (<it>Staphylococcus aureus, Enterococcus faecalis)</it>, and six Gram negative <it>(Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Shigella flexneri, Salmonella typhi) </it>and two fungal isolates (<it>Candida albicans, Candida krusei)</it>. The chemical composition was done according to Harbone (1976), the acute toxicity evaluation according to WHO protocol and the hepatic as well as serum parameters measured to assess liver and kidney functions.</p> <p>Results</p> <p>The chemical components of each plant's extract varied according to the solvent used, and they were found to contain alkaloids, flavonoids, polyphenols, triterpens, sterols, tannins, coumarins, glycosides, cardiac glycosides and reducing sugars. The methanolic and ethylacetate extracts of <it>Phyllanthus muellerianus </it>and <it>Piptadeniastum africana </it>presented the highest antimicrobial activities against all tested microorganisms with ID varying from 8 to 26 mm and MIC from 2.5 to 0.31 mg/ml. The <it>in vivo </it>acute toxicity study carried out on the methanolic extracts of <it>Phyllanthus muellerianus </it>and <it>Piptadeniastrum africana </it>indicated that these two plants were not toxic. At the dose of 4 g/kg body weight, kidney and liver function tests indicated that these two medicinal plants induced no adverse effect on these organs.</p> <p>Conclusion</p> <p>These results showed that, all these plant's extracts can be used as antimicrobial phytomedicines which can be therapeutically used against infections caused by multiresistant agents.</p> <p>Phyllanthus muellerianus, Piptadeniastum africana, antimicrobial, acute toxicity, kidney and liver function tests, Cameroon Traditional Medicine</p