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Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These-originally β-cell secretory products-extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function.Sea and marine biodiversity exploration represents a new frontier for the discovery of new natural products with human health benefits ("the exploitable biology", [...].Hippophae rhamnoides L. (Elaeagnaceae; commonly known as "sea buckthorn" and "vitamin tree"), is a spiny deciduous shrub whose fruit is used in foods and traditional medicines. The H. rhamnoides fruit (berry) is rich in vitamin C, with a level exceeding that found in lemons and oranges. H. rhamnoides berries are usually washed and pressed to create pomace and juice. Today, the powder of the aqueous extract of H. rhamnoides berries are sold as a functional food in many countries. As part of our ongoing effort to identify bioactive constituents from natural resources, we aimed to isolate and identify those from the fruits of H. rhamnoides. Phytochemical analysis of the extract of H. rhamnoides fruits led to the isolation and identification of six compounds, namely, a citric acid derivative (1), a phenolic (2), flavonoids (3 and 4), and megastigmane compounds (5 and 6). Treatment with compounds 1-6 did not have any impact on the cell viability of RAW 264.7 mouse macrophages. However, pretreatment with these compy inhibiting IKKα/β, I-κBα, NF-κB p65, iNOS, and COX-2, and the activities of IL-6 and TNF-α.Artificial vessels capable of long-term patency are essential clinical tools in vascular surgery that involves small vessels. On-going attempts to develop artificial vessels that complements restenosis have not been entirely successful. Here, we report on the fabrication of small-sized artificial vessels using a three-dimensional bio-printer. The fabrication employed biodegradable polycaprolactone and autologous MSCs harvested from the bone-marrow of canines. The MSCs were cultured and differentiated into endothelial-like cells. After confirming differentiation, artificial vessels comprising three-layers were constructed and implanted into the arteries of canines. The autologous MSCs printed on artificial vessels (cell-derived group) maintained a 64.3% patency (9 of 14 grafts) compared with artificial vessels without cells (control group, 54.5% patency (6 of 11 grafts)). The cell-derived vessels (61.9 cells/mm2 ± 14.3) had more endothelial cells on their inner surfaces than the control vessels (21 cells/mm2 ± 11.3). Moreover, the control vessels showed acute inflammation on the porous structures of the implanted artificial vessels, whereas the cell-derived vessels exhibited fibrinous clots with little to no inflammation. We concluded that the minimal rejection of these artificial vessels by the immune system was due to the use of autologous MSCs. We anticipate that this study will be of value in the field of tissue-engineering in clinical practice.In recent years, due to the dramatic increase in and global spread of bacterial resistance to a number of commonly used antibacterial agents, many studies have been directed at investigating drugs whose primary therapeutic purpose is not antimicrobial action. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, it is important to understand these antimicrobial effects and their potential clinical implications. Numerous studies report the antibacterial activity of non-steroidal anti-inflammatory drugs, local anaesthetics, phenothiazines such as chlorpromazine, levomepromazine, promethazine, trifluoperazine, methdilazine and thioridazine, antidepressants, antiplatelets and statins. Several studies have explored a possible protective effect of statins inreducing the morbidity and mortality of many infectious diseases. Various non-antibiotic agents exhibit antimicrobial activity via multiple and different mechanisms of action. Further studies are required in the field to further investigate these antimicrobial properties in different populations. This is of paramount importance in the antimicrobial resistance era, where clinicians have limited therapeutic options to combat problematic infections.Cancer patients are more susceptible to several bacterial infections, particularly urinary tract infections caused by uropathogenic E. coli (UPEC). The objective of this work was detection and the phylogenetic characterization of hospital-acquired isolates of uropathogenic E. coli in cancer patients and the determination of its relation with antibiotic resistance. A total of 110 uropathogenic E. coli responsible for hospital-acquired urinary tract infections in cancer patients were included in this study. A triplex PCR was employed to segregate different isolates into four different phylogenetic groups (A, B1, B2 and D). Drug resistance was evaluated by the disc diffusion method. All of the isolates were multiple drug-resistant (MDR) and 38.18% of all UPEC isolates were extended-spectrum beta-lactamase (ESBL) producers from which 52% were positive for the blaCTX-M gene, 40% for the blaTEM gene, and 17% for the blaSHVgene. Among 42 ESBL-producing uropathogenic E. selleck chemicals coli isolates, the majority belonged to phylogenetic group B2 (43%), followed by group D (36%), group A (19%) and group B1 (2%).
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