Activity

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. CompK mw In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame’s role in colorectal cancer.Iron homeostasis offers a significant bacterial vulnerability because pathogens obtain essential iron from their mammalian hosts, but host-defenses maintain vanishingly low levels of free iron. Although pathogens have evolved mechanisms to procure host-iron, these depend on well-regulated iron homeostasis. To disrupt iron homeostasis, our work has targeted iron mobilization from the iron storage protein bacterioferritin (BfrB) by blocking a required interaction with its cognate ferredoxin partner (Bfd). The blockade of the BfrB-Bfd complex by deletion of the bfd gene (Δbfd) causes iron to irreversibly accumulate in BfrB. In this study we used mass spectrometry and NMR spectroscopy to compare the proteomic response and the levels of key intracellular metabolites between wild type (wt) and isogenic ΔbfdP. aeruginosa strains. We find that the irreversible accumulation of unusable iron in BfrB leads to acute intracellular iron limitation, even if the culture media is iron-sufficient. Importantly, the iron limitation and concomitant iron metabolism dysregulation trigger a cascade of events that lead to broader metabolic homeostasis disruption, which includes sulfur limitation, phenazine-mediated oxidative stress, suboptimal amino acid synthesis and altered carbon metabolism.Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV’s “Achilles heel”, defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.A untargeted metabolomics approach was proposed in this study based on ultra-high performance liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) and rapid evaporative ionization mass spectrometry (REIMS) to discriminate lamb and mutton meat and investigate their subtle metabolic differences, considering the higher popularity of lamb meat than mutton in the market. Multivariate statistical analysis was performed for data processing in order to distinguish between the two sample types. A total of 42 potential metabolites (20 in positive and 22 in negative ion mode) were defined for UHPLC-QTOF analysis, which provided references for discriminating the two kinds of meat. Furthermore, three potential markers were tentatively identified using LC/MS data against chemical databases. In addition, 14 potential metabolites were putatively identified in negative ion mode using the LipidMaps database. Meanwhile, the data-driven soft independent modeling of class analogy (DD-SIMCA) model was established, which could rapidly differentiate non-pretreated lamb meat and mutton with 92% specificity, rendering REIMS a promising technique for meat identification.

to find the most up-to-date evidence of the effectiveness and safety of supervised physical therapy in polymyositis/dermatomyositis patients.

a systematic review of the literature in the main scientific databases was carried out. We searched for randomized controlled trials concerning supervised physical therapy and polymyositis/dermatomyositis. The PICOS method was used for the formulation of the clinical query. Methodological quality and the level of evidence of the included studies were assessed using the modified Jadad scale and the Oxford Centre for Evidence-Based Medicine Levels of Evidence guide, respectively.

a total of 2591 articles were found. By applying the inclusion/exclusion criteria, six randomized controlled clinical trials were admitted to the final phase of the review. The compared approaches concerned supervised exercise programs based on strategies of muscle strengthening or aerobic work. Following these exercises, an increase in the maximum rate of oxygen consumption, a decrease in to guide the choice towards different types of muscle contraction exercises.Enniatins (ENNs) that belong to the group of emerging mycotoxins are widespread contaminants of agricultural commodities. There is currently insufficient evidence to rule out health concerns associated with long-term exposure to ENNs and efforts must be strengthened to define a control strategy. While the potential of plant compounds to counteract the contamination with legislated mycotoxins has been reported, little remains known regarding ENNs. The present study evidenced for the first time the efficiency of hydroxycinnamic acids to inhibit the fungal growth and ENNs yield by Fusarium avenaceum. Notably, 0.5 mM of exogenous ferulic, caffeic, and p-coumaric acids led to a drastic reduction of ENNs synthesis in pH4 broths, with ferulic acid being the most potent. The ENNs production inhibitory activity of ferulic acid was shown to be associated with a significant down-regulation of the expression of ENNs biosynthetic genes. To further investigate the bioactivity of ferulic acid, its metabolic fate was characterized in fungal broths and the capacity of F.