Antibacterial, Anti-HIV-1 Protease and Cytotoxic Activities of Aqueous Ethanolic Extracts from Combretum Adenogonium Steud. Ex A. Rich (Combretaceae).

\ud \ud Records have shown that Combretum adenogonium Steud. Ex A. Rich (Combretaceae) is used in traditional medicine systems of several tribes in Tanzania. This study focused on the investigation of antibacterial activity, anti-HIV-1 protease activity, toxicity properties and classes of phytochemicals in extracts from C. adenogonium Steud. Ex A. Rich (Combretaceae) to evaluate potential of these extracts for development as herbal remedies. Dried plant material were ground to fine powder and extracted using 80% aqueous ethanol to afford root, leaf and stem bark extracts. The extracts were assayed for anti-HIV-1 protease activities, antibacterial activities using microdilution methods and cytotoxicity using brine shrimps lethality assay. Screening for major phytochemical classes was carried out using standard chemical tests. All extracts exhibited antibacterial activity to at least one of the test bacteria with MIC-values ranging from 0.31-5.0 mg/ml. Two extracts, namely, root and stem bark exhibited anti-HIV-1 PR activity with IC50 values of 24.7 and 26.5 μg/ml, respectively. Stem bark and leaf extracts showed mild toxicity with LC50 values of 65.768 μg/ml and 76.965 μg/ml, respectively, whereas roots were relatively non-toxic (LC50 = 110.042 μg/ml). Phytochemical screening of the extracts indicated presence of flavonoids, terpenoids, alkaloids, tannins, glycosides and saponins. These results provide promising baseline information for the potential development of C. adenogonium extracts in treatment of bacterial and HIV/AIDS-related opportunistic infections

Immune and hemorheological changes in Chronic Fatigue Syndrome

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. METHODS: Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56(dim)CD16(+ )and CD56(bright)CD16(-)) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed. RESULTS: CFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56(bright)CD16(- )NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56(dim)CD16(+ )NK cells were similar between the two groups. CONCLUSION: These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients

Coreceptor Usage by HIV-1 and HIV-2 Primary Isolates: The Relevance of CCR8 Chemokine Receptor as an Alternative Coreceptor

The human immunodeficiency virus replication cycle begins by sequential interactions between viral envelope glycoproteins with CD4 molecule and a member of the seven-transmembrane, G-protein-coupled, receptors' family (coreceptor). In this report we focused on the contribution of CCR8 as alternative coreceptor for HIV-1 and HIV-2 isolates. We found that this coreceptor was efficiently used not only by HIV-2 but particularly by HIV-1 isolates. We demonstrate that CXCR4 usage, either alone or together with CCR5 and/or CCR8, was more frequently observed in HIV-1 than in HIV-2 isolates. Directly related to this is the finding that the non-usage of CXCR4 is significantly more common in HIV-2 isolates; both features could be associated with the slower disease progression generally observed in HIV-2 infected patients. The ability of some viral isolates to use alternative coreceptors besides CCR5 and CXCR4 could further impact on the efficacy of entry inhibitor therapy and possibly also in HIV pathogenesis

Activation of Human T-Helper/Inducer Cell, T-Cytotoxic Cell, B-Cell, and Natural Killer (NK)-Cells and induction of Natural Killer Cell Activity against K562 Chronic Myeloid Leukemia Cells with Modified Citrus Pectin

<p>Abstract</p> <p>Background</p> <p>Modified citrus pectin (MCP) is known for its anti-cancer effects and its ability to be absorbed and circulated in the human body. In this report we tested the ability of MCP to induce the activation of human blood lymphocyte subsets like T, B and NK-cells.</p> <p>Methods</p> <p>MCP treated human blood samples were incubated with specific antibody combinations and analyzed in a flow cytometer using a 3-color protocol. To test functionality of the activated NK-cells, isolated normal lymphocytes were treated with increasing concentrations of MCP. Log-phase PKH26-labeled K562 leukemic cells were added to the lymphocytes and incubated for 4 h. The mixture was stained with FITC-labeled active form of caspase 3 antibody and analyzed by a 2-color flow cytometry protocol. The percentage of K562 cells positive for PKH26 and FITC were calculated as the dead cells induced by NK-cells. Monosaccharide analysis of the MCP was performed by high-performance anion-exchange chromatography with pulse amperometric detection (HPAEC-PAD).</p> <p>Results</p> <p>MCP activated T-cytotoxic cells and B-cell in a dose-dependent manner, and induced significant dose-dependent activation of NK-cells. MCP-activated NK-cells demonstrated functionality in inducing cancer cell death. MCP consisted of oligogalacturonic acids with some containing 4,5-unsaturated non-reducing ends.</p> <p>Conclusions</p> <p>MCP has immunostimulatory properties in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture. Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP.</p

Crosstalk between Chemokine Receptor CXCR4 and Cannabinoid Receptor CB2 in Modulating Breast Cancer Growth and Invasion

Cannabinoids bind to cannabinoid receptors CB(1) and CB(2) and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB(2) may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis.We observed high expression of both CB(2) and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB(2)-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4), highly metastatic clone of MDA-MB-231 (SCP2) and NT 2.5 cells (derived from MMTV-neu) by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems.This study provides novel insights into the crosstalk between CB(2) and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2) receptors could be used for developing innovative therapeutic strategies against breast cancer

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Pectic polysaccharides from Biophytum petersianum Klotzsch, and their activation of macrophages and dendritic cells

The Malian medicinal plant Biophytum petersianum Klotzsch (Oxalidaceae) is used as a treatment against various types of illnesses related to the immune system, such as joint pains, inflammations, fever, malaria, and wounds. A pectic polysaccharide obtained from a hot water extract of the aerial parts of B. petersianum has previously been reported to consist of arabinogalactans types I and II (AG-I and AG-II), probably linked to a rhamnogalacturonan backbone. We describe here further structural characteristics of the main polysaccharide fraction (BP1002) and fractions obtained by enzymatic degradations using endo -α-d-(1→4)-polygalacturonase (BP1002-I to IV). The results indicate that in addition to previously reported structures, rhamnogalacturan type II and xylogalacturonan areas appear to be present in the pectic polymer isolated from the plant. Atomic force microscopy confirmed the presence of branched structures, as well as a polydisperse nature. We further tested whether the BP1002 main fraction or the enzymatically degraded products could induce immunomodulating activity through stimulation of subsets of leukocytes. We found that macrophages and dendritic cells were activated by BP1002 fractions, while there was little response of T cells, B cells, and NK cells. The enzymatic treatment of the BP1002 main fraction gave important information on the structure-activity relations. It seems that the presence of rhamnogalacturonan type I is important for the bioactivity, as the bioactivity decreases with the decreased amounts of rhamnose, galactose, and arabinose. The demonstration of bioactivity by the plant extracts might indicate the mechanisms behind the traditional medical use of the plant. © The Author 2008. Published by Oxford University Press. All rights reserved

Unconventional methyl galactan synthesized via the thexyldimethylsilyl intermediate: Preparation, characterization, and properties

Reaction of a β-(1 → 4) linked galactan with TDMS chloride followed by methylation and desilylation yields methyl galactans with unconventional functionalization patterns. The products were characterized via FTIR and NMR of the intact polymer and by CE after controlled depolymerization. A TDMS-derivatized methyl galactan contains differently methylated secondary hydroxyl groups. SEC and analytical ultracentrifugation showed a consistent decrease in the molecular weight after the consecutive reaction steps. Biological studies revealed that the methyl galactans are less active in complement fixation assays as compared with a 3-O-methyl galactan-enriched polysaccharide fraction isolated from Acanthus ebracteatus. (Graph Presented) © 2008 Wiley-VCH Verlag GmbH & Co. KGaA