A Long Road for Stem Cells to Cure Sick Hearts: Update on Recent Clinical Trials

The contribution of stem cells to cure damaged hearts has finally been unraveled. A large number of preclinical and clinical studies have showed beneficial outcomes after myocardial infarction. In this review, the current understanding of stem cell therapy in preclinical and clinical experiences is summarized. Stem cells from bone marrow have shown a potential to improve cardiac performance after myocardial infarction in animal and early clinical studies. Clinical trials from all over the world have provided safety assessments of stem cell therapy with marginal improvement of clinical outcomes. Thus, further investigations should be encouraged to resolve the discrepancies between studies, clinical issues, and unclear translational findings. This review provides information and commentary on key trials for stem cell-based treat-ment of cardiovascular disease

A Cost-Effective ELP-Intein Coupling System for Recombinant Protein Purification from Plant Production Platform

BACKGROUND: Plant bioreactor offers an efficient and economical system for large-scale production of recombinant proteins. However, high cost and difficulty in scaling-up of downstream purification of the target protein, particularly the common involvement of affinity chromatography and protease in the purification process, has hampered its industrial scale application, therefore a cost-effective and easily scale-up purification method is highly desirable for further development of plant bioreactor. METHODOLOGY/PRINCIPAL FINDINGS: To tackle this problem, we investigated the ELP-intein coupling system for purification of recombinant proteins expressed in transgenic plants using a plant lectin (PAL) with anti-tumor bioactivity as example target protein and rice seeds as production platform. Results showed that ELP-intein-PAL (EiP) fusion protein formed novel irregular ER-derived protein bodies in endosperm cells by retention of endogenous prolamins. The fusion protein was partially self-cleaved in vivo, but only self-cleaved PAL protein was detected in total seed protein sample and deposited in protein storage vacuoles (PSV). The in vivo uncleaved EiP protein was accumulated up to 2-4.2% of the total seed protein. The target PAL protein could be purified by the ELP-intein system efficiently without using complicated instruments and expensive chemicals, and the yield of pure PAL protein by the current method was up to 1.1 mg/g total seed protein. CONCLUSION/SIGNIFICANCE: This study successfully demonstrated the purification of an example recombinant protein from rice seeds by the ELP-intein system. The whole purification procedure can be easily scaled up for industrial production, providing the first evidence on applying the ELP-intein coupling system to achieve cost-effective purification of recombinant proteins expressed in plant bioreactors and its possible application in industry

Integrated transcriptomic and proteomic analysis of the global response of Wolbachia to doxycycline-induced stress

The bacterium Wolbachia (order Rickettsiales), representing perhaps the most abundant vertically transmitted microbe worldwide, infects arthropods and filarial nematodes. In arthropods, Wolbachia can induce reproductive alterations and interfere with the transmission of several arthropod-borne pathogens. In addition, Wolbachia is an obligate mutualist of the filarial parasites that cause lymphatic filariasis and onchocerciasis in the tropics. Targeting Wolbachia with tetracycline antibiotics leads to sterilisation and ultimately death of adult filariae. However, several weeks of treatment are required, restricting the implementation of this control strategy. To date, the response of Wolbachia to stress has not been investigated, and almost nothing is known about global regulation of gene expression in this organism. We exposed an arthropod Wolbachia strain to doxycycline in vitro, and analysed differential expression by directional RNA-seq and label-free, quantitative proteomics. We found that Wolbachia responded not only by modulating expression of the translation machinery, but also by upregulating nucleotide synthesis and energy metabolism, while downregulating outer membrane proteins. Moreover, Wolbachia increased the expression of a key component of the twin-arginine translocase (tatA) and a phosphate ABC transporter ATPase (PstB); the latter is associated with decreased susceptibility to antimicrobials in free-living bacteria. Finally, the downregulation of 6S RNA during translational inhibition suggests that this small RNA is involved in growth rate control. Despite its highly reduced genome, Wolbachia shows a surprising ability to regulate gene expression during exposure to a potent stressor. Our findings have general relevance for the chemotherapy of obligate intracellular bacteria and the mechanistic basis of persistence in the Rickettsiales

Impact of chronic stress protocols in learning and memory in rodents: systematic review and meta-analysis

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals' strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests' performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.This work was funded by the European Commission (FP7) "SwitchBox" (Contract HEALTH-F2-2010-259772) project and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), and by Fundacao Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project "Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)"). PSM is supported by an FCT fellowship grant, from the PhD-iHES program, with the reference PDE/BDE/113601/2015.info:eu-repo/semantics/publishedVersio

No-reflow reversibility: a study based on serial assessment of multiple biomarkers

No-reflow after primary percutaneous coronary intervention (pPCI) may be reversible. 40 patients undergoing pPCI were evaluated by assessing either improvement or lack of changes regarding angiographic and electrocardiographic indexes of no-reflow between admission and pre-discharge. Myeloperoxidase (MPO; in nanograms per milliliter), C-reactive protein (CRP; in milligrams per liter), endothelin-1 (ET-1; in nanograms per milliliter), angiopoietin-2 (Ang-2, in picograms per milliliter), and their pre-discharge/basal values variations (\u394) were related to no-reflow evolution. \u394MPO and \u394CRP were greater in patients with sustained no-reflow or lack of ST-segment resolution (STR) as compared with those with reversible no-reflow or lack of STR (p\u2009=\u20090.033, p\u2009=\u20090.04, p\u2009<\u20090.001, and p\u2009=\u20090.001, respectively), whereas \u394ET-1 was similar in the two groups. \u394Ang-2 was greater in patients with sustained no-reflow or lack of STR as compared with those with reversible no-reflow or lack of STR (p\u2009=\u20090.01 and 0.044, respectively). Bigger \u394MPO, \u394CRP (increasing levels), and \u394Ang-2 (decreasing levels) are associated with sustained no-reflow, thus they might have a role in no-reflow evolution