Antifungal potential of extracts from three plants against two major pathogens of celery (apium graveolens l.) in Cameroon

With the aim of contributing to natural control of plant pathogens, the antifungal activity of 11 extracts from 3 Cameroonian plants namely, Drypetes gossweileri, Eucalyptus tereticornis and Sida acuta was evaluated against Acremonium apii and Colletotrichum dematium, respectively causal agents of brown spot and anthracnose diseases of celery (Apium graveolens L.). The supplemented media technique was used to assess the inhibition of both fungi mycelial growth by essential oils, ethanol,hot water and cold water extracts. The essential oils exhibited the highest antifungal activity at 50 ppm with essential oil from D. gossweileri; and 6000 ppm and 7000 ppm, against C. dematium and A. apii, respectively, with essential oil from E. tereticornis. Ethanol and aqueous extracts displayed a moderate inhibitory activity with the best activity obtained from D. gossweileri ethanol extracts (90.31% and 67.53%, respectively, against A. apii and C. dematium at 10000 ppm). The fungitoxic potential of essential oils was comparative to the synthetic fungicide used as positive control. Phytochemical screening of solvent extracts revealed a diverse composition in secondary metabolites and stronger inhibitory effects were recorded with extracts rich in alkaloids, phenols, anthraquinones and saponines. These findings suggest a promising potential of essential oils and ethanol extracts for botanicals control of celery fungal pathogens

Elevated Cell-Specific Microparticles Are a Biological Marker for Cerebral Dysfunctions in Human Severe Malaria

Cerebral malaria (CM) and severe anemia (SA) are the most severe complications of Plasmodium falciparum infections. Although increased release of endothelial microparticles (MP) correlates with malaria severity, the full extent of vascular cell vesiculation remains unknown. Here, we characterize the pattern of cell-specific MP in patients with severe malaria. We tested the hypothesis that systemic vascular activation contributes to CM by examining origins and levels of plasma MP in relation to clinical syndromes, disease severity and outcome. Patients recruited in Douala, Cameroon, were assigned to clinical groups following WHO criteria. MP quantitation and phenotyping were carried out using cell-specific markers by flow cytometry using antibodies recognizing cell-specific surface markers. Platelet, erythrocytic, endothelial and leukocytic MP levels were elevated in patients with cerebral dysfunctions and returned to normal by discharge. In CM patients, platelet MP were the most abundant and their levels significantly correlated with coma depth and thrombocytopenia. This study shows for the first time a widespread enhancement of vesiculation in the vascular compartment appears to be a feature of CM but not of SA. Our data underpin the role of MP as a biomarker of neurological involvement in severe malaria. Therefore, intervention to block MP production in severe malaria may provide a new therapeutic pathway

Antimycobacterial activity of selected medicinal plants extracts from Cameroon

New drugs are highly needed to control mycobacterial infections. This study aimed at screening ethnobotanically selected plants extracted using organic solvents for their antimycobacterial activity. In vitro assays were performed on Mycobacterium smegmatis, Mycobacterium avium, Mycobacterium bovis Bacille Calmette Guerin (BCG), Mycobacterium tuberculosis and Mycobacterium ulcerans using the Resazurin Microtiter Assay. Cytotoxicity was assessed on Human lung fibroblast cells (MRC5) and bone marrow-derived macrophages (BMDM) using the MTS tetrazolium assay. The most promising extract from Annickia chlorantha stem bark (ACsbI) was tested for intracellular antimycobacterial activity against M. smegmatis using infected BMDM. Sixty crude extracts, 19 fractions, and 2 purified compounds were obtained from 19 Cameroonian medicinal plants. Results showed that crude extracts mainly inhibited BCG, while interface fractions from A. chlorantha stem bark (ACsbI) and stem (ACstI) displayed the strongest activity against M. ulcerans, with Minimal Inhibitory Concentrations (MIC) of 1.95 and 7.81 µg/ml respectively. Two compounds purified from Sorindeia juglandifolia fruits (SJfr 3.6 and SJfr 4.5) showed activity against BCG and M. ulcerans at 3.9 µg/ml and 62.5 µg/ml respectively. Finally, ACsbI showed no toxicity against MRC5 cells and BMDM and inhibited the growth of intracellular M. smegmatis. The results achieved in this investigation support the traditional to use of these plants and the need to investigate them in deeper details to be able to find alternatives for the existing antimycobacterial drugs

Antibacterial and Antioxidant Properties of the Methanolic Extract of the Stem Bark of Pteleopsis hylodendron (Combretaceae)

Pteleopsis hylodendron (Combretaceae) is used in Cameroon and West Africa folk medicine for the treatment of various microbial infections (measles, chickenpox, and sexually transmitted diseases). The antibacterial properties of the methanolic extract and fractions from stem bark of Pteleopsis hylodendron were tested against three Gram-positive bacteria and eight Gram-negative bacteria using Agar-well diffusion and Broth microdilution methods. Antioxidant activities of the crude extract and fractions were investigated by DPPH radical scavenging activity and β-carotene-linoleic acid assays. The methanolic extract and some fractions exhibited antibacterial activities that varied between the bacterial species (ID = 0.00–25.00 mm; MIC = 781–12500 μg/mL and 0.24–1000 μg/mL). The activity of the crude extract is, however, very weak compared to the reference antibiotics (MIC = 0.125–128 μg/mL). Two fractions (FE and FF) showed significant activity (MIC = 0.97 μg/mL) while S. aureus ATCC 25922 was almost resistant to all the tested fractions. In addition, the crude extract and some fractions showed good antioxidant potential with inhibition values ranging from 17.53 to 98.79%. These results provide promising baseline information for the potential use of this plant as well as some of the fractions in the treatment of infectious diseases and oxidative stress

The Woody Guthrie Centennial Bibliography

This bibliography updates two extensive works designed to include comprehensively all significant works by and about Woody Guthrie. Richard A. Reuss published A Woody Guthrie Bibliography, 1912–1967 in 1968 and Jeffrey N. Gatten\u27s article “Woody Guthrie: A Bibliographic Update, 1968–1986” appeared in 1988. With this current article, researchers need only utilize these three bibliographies to identify all English-language items of relevance related to, or written by, Guthrie

Antiplasmodial volatile extracts from Cleistopholis patens Engler & Diels and Uvariastrum pierreanum Engl. (Engl. & Diels) (Annonaceae) growing in Cameroon

In a search for alternative treatment for malaria, plant-derived essential oils extracted from the stem barks and leaves of Cleistopholis patens and Uvariastrum pierreanum (Annonaceae) were evaluated in vitro for antiplasmodial activity against the W2 strain of Plasmodium falciparum. The oils were obtained from 500 g each of stem barks and leaves, respectively, by hydrodistillation, using a Clevenger-type apparatus with the following yields: 0.23% and 0.19% for C. patens and 0.1% and 0.3% for U. pierreanum (w/w relative to dried material weight). Analysis of 10% (v/v) oil in hexane by gas chromatography and mass spectrometry identified only terpenoids in the oils, with over 81% sesquiterpene hydrocarbons in C. patens extracts and U. pierreanum stem bark oil, while the leaf oil from the latter species was found to contain a majority of monoterpenes. For C. patens, the major components were α-copaene, δ-cadinene, and germacrene D for the stem bark oil and β-caryophyllene, germacrene D, and germacrene B for the leaf oil. The stem bark oil of U. pierreanum was found to contain mainly β-bisabolene and α-bisabolol, while α- and β-pinenes were more abundant in the leaf extract. Concentrations of oils obtained by diluting 1-mg/mL stock solutions were tested against P. falciparum in culture. The oils were active, with IC50 values of 9.19 and 15.19 μg/mL for the stem bark and leaf oils, respectively, of C. patens and 6.08 and 13.96 μg/mL, respectively, for those from U. pierreanum. These results indicate that essential oils may offer a promising alternative for the development of new antimalarials

Effect of market orientation, network capability and entrepreneurial orientation on international performance of small and medium enterprises (SMEs)

ABSTRACT: This study contributes to literature on the internationalization of SMEs by analysing the influence of International Market Orientation, Network Capability, and International Entrepreneurial Orientation on the International Performance of this kind of businesses. Particularly, both the direct effects of explanatory variables of international Performance and interdependence relations between them are analysed. Results obtained from a sample of 161 Mexican SMEs using SEM-PLS analysis show that the International Performance of this kind of businesses is favourably influenced by their Network Capability and International Entrepreneurial Orientation, but not by their International Market Orientation. Similarly, it is verified that interdependence relations exist among the explanatory variables of International Performance of SMEs, where positive impact of International Entrepreneurial Orientation is observed on Network Capability and the International Market Orientation of SMEs

MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma

BACKGROUND: Through negative regulation of gene expression, microRNAs (miRNAs) can function in cancers as oncosuppressors, and they can show altered expression in various tumor types. Here we have investigated medulloblastoma tumors (MBs), which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many cell-fate-determining stages. MBs occur bimodally, with the peak incidence seen between 3-4 years and 8-9 years of age, although it can also occur in adults. Notch regulates a subset of the MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulated these phenomena, and can be used in anti-cancer therapies. METHODOLOGY/PRINCIPAL FINDINGS: In a screening of MB cell lines, the miRNA miR-199b-5p was seen to be a regulator of the Notch pathway through its targeting of the transcription factor HES1. Down-regulation of HES1 expression by miR-199b-5p negatively regulates the proliferation rate and anchorage-independent growth of MB cells. MiR-199b-5p over-expression blocks expression of several cancer stem-cell genes, impairs the engrafting potential of MB cells in the cerebellum of athymic/nude mice, and of particular interest, decreases the MB stem-cell-like (CD133+) subpopulation of cells. In our analysis of 61 patients with MB, the expression of miR-199b-5p in the non-metastatic cases was significantly higher than in the metastatic cases (P = 0.001). Correlation with survival for these patients with high levels of miR-199b expression showed a positive trend to better overall survival than for the low-expressing patients. These data showing the down-regulation of miR-199b-5p in metastatic MBs suggest a potential silencing mechanism through epigenetic or genetic alterations. Upon induction of de-methylation using 5-aza-deoxycytidine, lower miR-199b-5p expression was seen in a panel of MB cell lines, supported an epigenetic mechanism of regulation. Furthermore, two cell lines (Med8a and UW228) showed significant up-regulation of miR-199b-5p upon treatment. Infection with MB cells in an induced xenograft model in the mouse cerebellum and the use of an adenovirus carrying miR-199b-5p indicate a clinical benefit through this negative influence of miR-199b-5p on tumor growth and on the subset of MB stem-cell-like cells, providing further proof of concept. CONCLUSIONS/SIGNIFICANCE: Despite advances in our understanding of the pathogenesis of MB, one-third of these patients remain incurable and current treatments can significantly damage long-term survivors. Here we show that miR-199b-5p expression correlates with metastasis spread, identifying a new molecular marker for a poor-risk class in patients with MB. We further show that in a xenograft model, MB tumor burden can be reduced, indicating the use of miR199b-5p as an adjuvant therapy after surgery, in combination with radiation and chemotherapy, for the improvement of anti-cancer MB therapies and patient quality of life. To date, this is the first report that expression of a miRNA can deplete the tumor stem cells, indicating an interesting therapeutic approach for the targeting of these cells in brain tumors

Pattern of Relapse and Treatment Response in WNT- Activated Medulloblastoma

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses