Kinetic study of nordihydroguaiaretic acid recovery from Larrea tridentata by microwave-assisted extraction

Nordihydroguaiaretic acid (NDGA) is a powerful antioxidant that can be found in plants like Larrea tridentata (Zygophyllaceae), also known as creosote bush, which grows in semidesert areas of Southwestern United States and Northern Mexico [1]. Several studies have demonstrated that NDGA has important biological activities with great interest in the health area, such as antiviral, cancer chemopreventive, and antitumorgenic activities [2]. Extraction of bioactive compounds from plants is conventionally performed using a heat‐reflux extraction method. However, different techniques have been developed in order to decrease extraction time and solvent consumption, as well as to increase the extraction yield and enhance the extracts quality [3]. The objective of this study was to develop a microwave‐assisted extraction (MAE) method for NDGA recovery from Larrea tridentata leaves, and compare the obtained results with those found by using the conventional heat‐reflux extraction (HRE)

Exploitation of Mexican agro industrial wastes as raw material for solid-state fermentation processes

Annually, large volumes of wastes are produced by food, agricultural and forestry industries, which if disposed cause serious environmental problems. Therefore, it is of great importance to find alternative ways to reuse them. Due to the composition rich in sugars, which due to their organic nature are easily assimilated by the microorganisms; such wastes could be appropriate for use as raw materials in the production of industrially-relevant compounds under solid-state fermentation (SSF) conditions. However, the physical-chemical and microbiological characteristics of the solid substrate affect the efficiency of the SSF process. In the present study, ten different agro industrial wastes derived from Mexican local regions were evaluated for use as raw material in SSF. The wastes included creosote bush leaves (Larrea tridentata), variegated Caribbean agave (Agave lechuguilla), lemon peel (Citrus aurantifolia), orange peel (Citrus sinensis), apple pomace (Malus domestica), pistachio shell (Pistacia vera), wheat bran (Triticum spp.), coconut husk (Cocos nucífera), pecan nutshell (Carya illinoinensis), and bean residues (Phaseolus vulgaris). All of them were physical-chemically and microbiologically characterized. Physical-chemical tests consisted in the determination of the critical humidity point (CHP) and the water absorption index (WAI), while the microbiological tests were based on the evaluation of Aspergillus niger Aa-20 growth rate in such materials. The study pointed out that coconut husk, apple pomace, lemon and orange peels have great potential to be successfully used as raw material in SSF, since they have low water content linked to the structure (that is ideal to easily adjust the water content according to the process to be used), and allowed good and fast microorganism growth. Their use in SSF would be an interesting alternative to add value to these residues besides to be of great economical advantage and an environmental-friendly way for waste management.info:eu-repo/semantics/publishedVersio

Biological Activity and Implications of the Metalloproteinases in Diabetic Foot Ulcers

Inadequate metabolic control predisposes diabetic patient to a series of complications on account of diabetes mellitus (DM). Among the most common complications of DM is neuropathy, which causes microvascular damage by hyperglycemia in the lower extremities which arrives characterized by a delayed closing. The global prevalence of diabetic neuropathy (DN) was 66% of people with diabetes in 2015, representing the principal cause of total or partial lower extremities amputation, with 22.6% of the patients with DN. Matrix metalloproteinases (MMPs) are involved in healing. The function that these mainly play is the degradation during inflammation that has as consequence the elimination of the extracellular matrix (ECM), the disintegration of the capillary membrane to give way to angiogenesis and cellular migration for the remodeling of damaged tissue. The imbalance in MMPs may increase the chronicity of a wound, what leads to chronic foot ulcers and amputation. This chapter focuses on the role of MMPs in diabetic wound healing

Targeting of SUMO substrates to a Cdc48-Ufd1-Npl4 segregase and STUbL pathway in fission yeast

In eukaryotes, the conjugation of proteins to the small ubiquitin-like modifier (SUMO) regulates numerous cellular functions. A proportion of SUMO conjugates are targeted for degradation by SUMO-targeted ubiquitin ligases (STUbLs) and it has been proposed that the ubiquitin-selective chaperone Cdc48/p97-Ufd1-Npl4 facilitates this process. However, the extent to which the two pathways overlap, and how substrates are selected, remains unknown. Here we address these questions in fission yeast through proteome-wide analyses of SUMO modification sites. We identify over a thousand sumoylated lysines in a total of 468 proteins and quantify changes occurring in the SUMO modification status when the STUbL or Ufd1 pathways are compromised by mutations. The data suggest the coordinated processing of several classes of SUMO conjugates, many dynamically associated with centromeres or telomeres. They provide new insights into subnuclear organization and chromosome biology, and, altogether, constitute an extensive resource for the molecular characterization of SUMO function and dynamics

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe