Antifungal and physicochemical properties of Ocimum essential oil loaded in poly(lactic acid) nanofibers

Poly(lactic acid) (PLA) nanofibres containing different proportions of the essential oils from Ocimum basilicum L. and Ocimum gratissimum L. were prepared by solution blow spinning method. The essential oils were extracted by hydrodistillation and characterized by gas chromatography. MEV, contact angle, DSC and FTIR were used to characterize the nanofibres. The effect of bioative nanofibres on the growth of the fungus and on the production of ochratoxin A were evaluated using the fumigation test. Linalool, 1·8-cineole and camphor were the principal components of the essential oil from O. basilicum, and eugenol was the principal constituent in the oil from O. gratissimum. An increase in the average diameter of the nanofibres was observed with the addition of the essential oils. The essential oils acted as a plasticizer, resulting in a reduction in the crystallinity of the PLA. The encapsulation of essential oils in PLA nanofibres was verified by FTIR. An effective antifungal and antimicotoxygenic activity against Aspergillus ochraceus and Aspergillus westerdjikiae was observed for the bioative nanofibres. These results confirm the potential of PLA nanofibres containing the essential oils for the control of toxigenic fungi that cause the deterioration of food and are harmful to human health.     

A meta-analysis of molecular marker genetic datasets for eastern Africa trees supports the utility of potential natural vegetation maps for planning climate-smart restoration initiatives

Tree Genetics & Genomes - Forest and woodland landscape restoration is a key undertaking of renewed interest for forestry and conservation practitioners, but is hampered by the lack of...     

Multi-Tiered Observation and Response Charts: Prevalence and Incidence of Triggers,Modifications and Calls,to Acutely Deteriorating Adult Patients

Background

Observation charts are the primary tool for recording patient vital signs. They have a critical role in documenting triggers for a multi-tiered escalation response to the deteriorating patient. The objectives of this study were to ascertain the prevalence and incidence of triggers, trigger modifications and escalation response (Call) amongst general medical and surgical inpatients following the introduction of an observation and response chart (ORC).

Methods

Prospective (prevalence), over two 24-hour periods, and retrospective (incidence), over entire hospital stay, observational study of documented patient observations intended to trigger one of three escalation responses, being a MER—Medical Emergency Response [highest tier], MDT—Multidisciplinary Team [admitting team], or Nurse—senior ward nurse [lowest tier] response amongst adult general medical and surgical patients.

Results

Prevalence: 416 patients, 321 (77.2%) being medical admissions, median age 76 years (IQR 62, 85) and 95 (22.8%) Not for Resuscitation (NFR). Overall, 193 (46.4%) patients had a Trigger, being 17 (4.1%) MER, 45 (10.8%) MDT and 178 (42.8%) Nurse triggers. 60 (14.4%) patients had a Call, and 72 (17.3%) a modified Trigger. Incidence: 206 patients, of similar age, of whom 166 (80.5%) had a Trigger, 122 (59.2%) a Call, and 91 (44.2%) a modified Trigger. Prevalence and incidence of failure to Call was 33.2% and 68% of patients, respectively, particular for Nurse Triggers (26.7% and 62.1%, respectively). The number of Modifications, Calls, and failure to Call, correlated with the number of Triggers (0.912 [p<0.01], 0.631 [p<0.01], 0.988 [p<0.01]).

Conclusion

Within a multi-tiered response system for the detection and response to the deteriorating patient Triggers, their Modifications and failure to Call are common, particularly within the lower tiers of escalation. The number of Triggers and their Modifications may erode the structure, compliance, and potential efficacy of structured observation and response charts within a multi-tiered response system.     

Modulation of Fas-dependent apoptosis: a dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cells

We have previously shown that regulatory CD25(+)CD4(+) T cells are resistant to clonal deletion induced by viral superantigen in vivo. In this work we report that isolated CD25(+)CD4(+) T cells activated in vitro by anti-CD3 Ab are resistant to Fas-induced apoptosis, in contrast to their CD25(-)CD4(+) counterparts. Resistance of CD25(+)CD4(+) T cells to Fas-dependent activation-induced cell death is not linked to their inability to produce IL-2 or to their ability to produce IL-10. The sensitivity of both populations to Fas-induced apoptosis can be modulated in vitro by changing the CD25(+)CD4(+):CD25(-)CD4(+) T cell ratio. The sensitivity of CD25(-)CD4(+) T cells to apoptosis can be reduced, while the sensitivity of CD25(+)CD4(+) T cells can be enhanced. Modulation of Fas-dependent apoptosis is associated with changes in cytokine production. However, while CD25(-)CD4(+) T cell apoptosis is highly dependent on IL-2 (production of which is inhibited by CD25(+)CD4(+) T cells in coculture), modulation of CD25(+)CD4(+) T cell apoptosis is IL-2 independent. Taken together, these results suggest that CD25(+)CD4(+) and CD25(-)CD4(+) T cell sensitivity to Fas-dependent apoptosis is dynamically modulated during immune responses; this modulation appears to help maintain a permanent population of regulatory T cells required to control effector T cells.     

Effects of Anabolic Steroids and High-Intensity Aerobic Exercise on Skeletal Muscle of Transgenic Mice

In an attempt to shorten recovery time and improve performance, strength and endurance athletes occasionally turn to the illicit use of anabolic-androgenic steroids (AAS). This study evaluated the effects of AAS treatment on the muscle mass and phenotypic characteristics of transgenic mice subjected to a high-intensity, aerobic training program (5d/wk for 6 weeks). The transgenic mice (CETP^+/-LDLr^-/+) were engineered to exhibit a lipid profile closer to humans. Animals were divided into groups of sedentary (Sed) and/or training (Ex) mice (each treated orally with AAS or gum arabic/vehicle: Sed-C, Sed-M, ex-C, ex-M). The effects of AAS (mesterolone: M) on specific phenotypic adaptations (muscle wet weight, cross-sectional area, and fiber type composition) in three hindlimb muscles (soleus:SOL, tibialis anterior:TA and gastrocnemius:GAS) were assessed. In order to detect subtle changes in fiber type profile, the entire range of fiber types (I, IC, IIAC, IIA, IIAD, IID, IIDB, IIB) was delineated using mATPase histochemistry. Body weight gain occurred throughout the study for all groups. However, the body weight gain was significantly minimized with exercise. This effect was blunted with mesterolone treatment. Both AAS treatment (Sed-M) and high-intensity, aerobic training (ex-C) increased the wet weights of all three muscles and induced differential hypertrophy of pure and hybrid fibers. Combination of AAS and training (ex-M) resulted in enhanced hypertrophy. In the SOL, mesterolone treatment (Sed-M and ex-M) caused dramatic increases in the percentages of fiber types IC, IIAC, IIAD, IID, with concomitant decrease in IIA, but had minimal impact on fiber type percentages in the predominantly fast muscles. Overall, the AAS-induced differential adaptive changes amounted to significant fiber type transformations in the fast-to-slow direction in SOL. AAS treatment had a significant effect on muscle weights and fiber type composition in SOL, TA and GAS which was even maximized in animals subjected to metabolically high-intensity aerobic exercise.     

EGFR inhibitors exacerbate differentiation and cell cycle arrest induced by retinoic acid and vitamin D3 in acute myeloid leukemia cells

By means of an unbiased, automated fluorescence microscopy-based screen, we identified the epidermal growth factor receptor (EGFR) inhibitors erlotinib and gefitinib as potent enhancers of the differentiation of HL-60 acute myeloid leukemia (AML) cells exposed to suboptimal concentrations of vitamin A (all-trans retinoic acid, ATRA) or vitamin D (1α,25-hydroxycholecalciferol, VD). Erlotinib and gefitinib alone did not promote differentiation, yet stimulated the acquisition of morphological and biochemical maturation markers (including the expression of CD11b and CD14 as well as increased NADPH oxidase activity) when combined with either ATRA or VD. Moreover, the combination of erlotinib and ATRA or VD synergistically induced all the processes that are normally linked to terminal hematopoietic differentiation, namely, a delayed proliferation arrest in the G₀/G₁ phase of the cell cycle, cellular senescence, and apoptosis. Erlotinib potently inhibited the (auto)phosphorylation of mitogen-activated protein kinase 14 (MAPK14, best known as p38^MAPK) and SRC family kinases (SFKs). If combined with the administration of ATRA or VD, the inhibition of p38^MAPK or SFKs with specific pharmacological agents mimicked the pro-differentiation activity of erlotinib. These data were obtained with 2 distinct AML cell lines (HL-60 and MOLM-13 cells) and could be confirmed on primary leukemic blasts isolated from the circulation of AML patients. Altogether, these findings point to a new regimen for the treatment of AML, in which naturally occurring pro-differentiation agents (ATRA or VD) may be combined with EGFR inhibitors.     

High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal,Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications

MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options.     

DEVELOPMENTAL CHANGES IN Na+, K+ AND ATP AND IN THE LEVELS AND TRANSPORT OF AMINO ACIDS IN INCUBATED SLICES OF RAT BRAIN

Abstract—

• 1 Upon incubation, slices of brain tissue took up fluid; the degree of swelling increased with increasing age. No sweiling occurred in slices from foetal brain. Since this swelling was associated with increases in the inulin space, the percentage of inulin space in slices at the end of incubation increased during brain development.
• 2 Most of the capacity for ion transport seemed to be absent from foetal brain. In vivo and in slices, Na⁺ was very high and K⁺ was very low in comparison to levels at other ages. There was a rapid change around birth, but no significant change at later ages. Upon incubation, Na⁺ levels increased in other slices, but not in slices of foetal brain.
• 3 Upon incubation of the slices, ATP levels were restored to levels close to those in the living brain; there were no significant alterations in available energy during development to explain changes in amino acid transport.
• 4 The composition of the free pool of cerebral amino acids in vivo changed with development, with some compounds (glutamic acid and related compounds) increasing, others (mostly‘essential’amino acids) decreasing, with age. These changes were not linear with time, and the level of a compound might exhibit several peaks during development.
• 5 The uptake (influx) of taurine, glutamate and glycine into brain slices increased rapidly during the foetal and early neonatal periods, reached a maximum between 2 and 3 weeks of postnatal age and then declined to adult levels. The levels of steady-state uptake with glycine also exhibited a maximal peak at 2-3 weeks of postnatal age. Steady-state uptake of taurine and glutamate reached adult levels by about 3 weeks of age.
• 6 The pattern of inhibition of amino acid transport by two specific amino acid analogues changed during development for some amino acids (GABA, glycine and glutamate), indicating an alteration in substrate specificity.
• 7 The results demonstrate complex changes in cerebral amino acid transport during development, with several maxima or minima and with changes in specificity for at least some compounds.