Antimicrobial cationic peptides are of interest because they can combat multi-drug-resistant microbes. Most peptides form alpha-helices or beta-sheet-like structures that can insert into and ...subsequently disintegrate negatively charged bacterial cell surfaces. Here, we show that a novel class of core-shell nanoparticles formed by self-assembly of an amphiphilic peptide have strong antimicrobial properties against a range of bacteria, yeasts and fungi. The nanoparticles show a high therapeutic index against Staphylococcus aureus infection in mice and are more potent than their unassembled peptide counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show that the nanoparticles can cross the blood-brain barrier and suppress bacterial growth in infected brains. Taken together, these nanoparticles are promising antimicrobial agents that can be used to treat brain infections and other infectious diseases.
Introduction of hydrophilic components, particularly amines and zwitterions, onto a degradable polymer platform, while maintaining precise control over the polymer composition, has been a challenge. ...Recognizing the importance of these hydrophilic residues in multiple aspects of the nanobiomedicine field, herein, a straightforward synthetic route to access well-defined amphiphilic and hydrophilic degradable block copolymers from diethanolamine-derived functional eight-membered N-substituted aliphatic cyclic carbonates is reported. By this route, tertiary amine, secondary amine, and zwitterion residues can be incorporated across the polymer backbone. Demonstration of pH-responsiveness of these hydrophilic residues and their utility in the development of drug-delivery vehicles, catered for the specific requirements of respective model drugs (doxorubicin and diclofenac sodium salt) are shown. As hydrophilic components in degradable polymers play crucial roles in the biological interactions, these materials offers opportunities to expand the scope and applicability of aliphatic cyclic carbonates. Our approach to these functional polycarbonates will expand the range of biocompatible and biodegradable synthetic materials available for nanobiomedicine, including drug and gene delivery, antimicrobials, and hydrophilic polymers as poly(ethylene glycol) (PEG) alternatives.
Malignant ascites presents a considerable clinical challenge to the management of ovarian cancer, but also provides a wealth of opportunities for translational research. The accessibility of ascitic ...fluid and its cellular components make it an excellent source of tumour tissue for the investigation of prognostic and predictive biomarkers, pharmacodynamic markers and for molecular profiling analysis. In this Opinion article, we discuss recent advances in our understanding of its pathophysiology, the development of new methods to characterize its molecular features and how these findings can be used to improve the treatment of malignant ascites, particularly in the context of ovarian cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is ...currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future.
Highlights • Developmental disruptions of serotonin signaling involved in autism. • Hyperserotonemia provokes a loss of serotonin terminals. • Deficiency of the serotonergic system induces mis-wiring ...of neural network.
The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this ...study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30-45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
To utilize transgenic GMR‐Aβ42 Drosophila melanogaster as a model to evaluate potential Alzheimer’s disease (AD)‐reversal effects via the administration of lactic acid bacteria (LAB) strains, ...and associations of LAB with changes in gut microbiota profiles.
Methods and Results
Wild‐type flies (Oregon‐R) were crossed with glass multimer reporter‐GAL4 (GMR‐GAL4) to produce GMR‐OreR (Control), while UAS‐Aβ42 (#33769) were crossed with GMR‐GAL4 to produce transgenic Drosophila line that expressed Aβ42 (GMR‐Aβ42). Feed containing seven different LAB strains (Lactobacillus paracasei 0291, Lactobacillus helveticus 1515, Lactobacillus reuteri 30242, L. reuteri 8513d, Lactobacillus fermentum 8312, Lactobacillus casei Y, Lactobacillus sakei Probio65) were given to GMR‐Aβ42 respectively, while feed without LAB strains were given to control and transgenic GMR‐Aβ42.nf Drosophila lines. The morphology of the eyes was viewed with scanning electron microscopy (SEM). The changes in gut microbiota profiles associated with LAB were analysed using 16s high throughput sequencing. Malformation of eye structures in transgenic GMR‐Aβ42 Drosophila were reversed upon the administration of LAB strains, with more prevalent effects from L. sakei Probio65 and L. paracasei 0291. The GMR‐Aβ42.nf group showed dominance of Wolbachia in the gut, a genus that was almost absent in the normal control group (P < 0·05). The administration of L. sakei Probio65 and L. paracasei 0291 reduced the abundance of Wolbachia accompanied by increased abundance of Stenotrophomonas and Acetobacter (P < 0·05), resembling the microbial profile of the control group.
Conclusions
Lactobacillus sakei Probio65 and Lactobacillus paracasei 0291 have more prominent effects in reversing malformed eye of transgenic GMR‐Aβ42 Drosophila, and reducing the abundance of Wolbachia accompanied by an increased abundance of Stenotrophomonas and Acetobacter.
Significance and Impact of the Study
Potentials of LAB to prevent and/or alleviate the onset and pathogenesis of neurodegenerative diseases such as AD, supporting brain health strategies along the gut–brain axis.
Background
Several associations between microsatellite instability (MSI) and other clinicopathological factors have been reported in gastric cancer, but the results have been ambiguous. This ...systematic review and meta‐analysis investigated the relationship between MSI and overall survival and clinicopathological characteristics of patients with gastric cancer.
Methods
A systematic literature search of the PubMed, Cochrane and Ovid databases until 31 January 2016 was performed in accordance with the PRISMA statement. The articles were screened independently according to PICO (population, intervention, comparator, outcome) eligibility criteria. All eligible articles were evaluated independently by two reviewers for risk of bias according to the Quality In Prognosis Study tool.
Results
Overall, 48 studies with a total of 18 612 patients were included. MSI was found in 9·2 per cent of patients (1718 of 18 612), and was associated with female sex (odds ratio (OR) 1·57, 95 per cent c.i. 1·31 to 1·89; P < 0·001), older age (OR 1·58, 2·20 to 1·13; P < 0·001), intestinal Laurén histological type (OR 2·23, 1·94 to 2·57; P < 0·001), mid/lower gastric location (OR 0·38, 0·32 to 0·44; P < 0·001), lack of lymph node metastases (OR 0·70, 0·57 to 0·86, P < 0·001) and TNM stage I–II (OR 1·77, 1·47 to 2·13; P < 0·001). The pooled hazard ratio for overall survival of patients with MSI versus those with non‐MSI gastric cancer from 21 studies was 0·69 (95 per cent c.i. 0·56 to 0·86; P < 0·001).
Conclusion
MSI in gastric cancer was associated with good overall survival, reflected in several favourable clinicopathological tumour characteristics.
Microsatellite instabililty subgroup does better
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