Application of metabolomics in diagnostics and differentiation of meningitis: A narrative review with a critical approach to the literature.

Due to its high mortality rate associated with various life-threatening sequelae, meningitis poses a vital problem in contemporary medicine. Numerous algorithms, many of which were derived with the aid of artificial intelligence, were brought up in a strive for perfection in predicting the status of sepsis-related survival or exacerbation. This review aims to provide key insights on the contextual utilization of metabolomics. The aim of this the metabolomic approach set of methods can be used to investigate both bacterial and host metabolite sets from both the host and its microbes in several types of specimens - even in one's breath, mainly with use of two methods - Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR). Metabolomics, and has been used to elucidate the mechanisms underlying disease development and metabolic identification changes in a wide range of metabolite contents, leading to improved methods of diagnosis, treatment, and prognosis of meningitis. Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) are the main analytical platforms used in metabolomics. Its high sensitivity accounts for the usefulness of metabolomics in studies into meningitis, its sequelae, and concomitant comorbidities. Metabolomics approaches are a double-edged sword, due to not only their flexibility, but also - high complexity, as even minor changes in the multi-step methods can have a massive impact on the results. Information on the differential diagnosis of meningitis act as a background in presenting the merits and drawbacks of the use of metabolomics in context of meningeal infections.

Modulators of cellular cholesterol homeostasis as antiproliferative and model membranes perturbing agents.

Cholesterol is an important component of mammalian cell membranes affecting their fluidity and permeability. Together with sphingomyelin, cholesterol forms microdomains, called lipid rafts. They play important role in signal transduction forming platforms for interaction of signal proteins. Altered levels of cholesterol are known to be strongly associated with the development of various pathologies (e.g., cancer, atherosclerosis and cardiovascular diseases). In the present work, the group of compounds that share the property of affecting cellular homeostasis of cholesterol was studied. It contained antipsychotic and antidepressant drugs, as well as the inhibitors of cholesterol biosynthesis, simvastatin, betulin, and its derivatives. All compounds were demonstrated to be cytotoxic to colon cancer cells but not to non-cancerous cells. Moreover, the most active compounds decreased the level of free cellular cholesterol. The interaction of drugs with raft-mimicking model membranes was visualized. All compounds reduced the size of lipid domains, however, only some affected their number and shape. Membrane interactions of betulin and its novel derivatives were characterized in detail. Molecular modeling indicated that high dipole moment and significant lipophilicity were characteristic for the most potent antiproliferative agents. The importance of membrane interactions of cholesterol homeostasis-affecting compounds, especially betulin derivatives, for their anticancer potency was suggested.

Motor Overflow during Reaching in Infancy: Quantification of Limb Movement Using Inertial Motion Units.

Early in life, infants exhibit motor overflow, which can be defined as the generation of involuntary movements accompanying purposeful actions. We present the results of a quantitative study exploring motor overflow in 4-month-old infants. This is the first study quantifying motor overflow with high accuracy and precision provided by Inertial Motion Units. The study aimed to investigate the motor activity across the non-acting limbs during goal-directed action. To this end, we used wearable motion trackers to measure infant motor activity during a baby-gym task designed to capture overflow during reaching movements. The analysis was conducted on the subsample of participants (n = 20), who performed at least four reaches during the task. A series of Granger causality tests revealed that the activity differed depending on the non-acting limb and the type of the reaching movement. Importantly, on average, the non-acting arm preceded the activation of the acting arm. In contrast, the activity of the acting arm was followed by the activation of the legs. This may be caused by their distinct purposes in supporting postural stability and efficiency of movement execution. Finally, our findings demonstrate the utility of wearable motion trackers for precise measurement of infant movement dynamics.

Longitudinal changes in infants' rhythmic arm movements during rattle-shaking play with mothers.

From early on, infants produce a variety of rhythmic behaviors-an ability that likely supports later social communication. However, it is unclear, how this rhythmic motor production changes with age. Here, we investigated the coupling between infants' arm movements across the first year of life in a social context of a rattle-shaking play with their mothers. Through longitudinal measurements at 4, 6, 9, and 12 months of age using wearable motion trackers placed on infants' arms, we show that infants (N = 40) are similarly motivated to attempt rattle-shaking across the first year of life. However, with age, they make more rattling movements with an increased frequency. Their left and right arm movements become more coupled during rattle-shaking, as shown by an increase in wavelet coherence. Infants produced more rattling movements when they were rattling alone than when their mothers were rattling or singing simultaneously. There were no differences between infants' individual and social rattling in between-arms coherence. Our results may help to understand rhythmic arm movements as precursors of motor social coordination.

Application of Metabolomics in Childhood Leukemia Diagnostics.

Metabolomics is a new field of science dealing with the study and analysis of metabolites formed in living cells. The biological fluids used in this test method are: blood, blood plasma, serum, cerebrospinal fluid, saliva and urine. The most popular methods of assessing the composition of metabolites include nuclear magnetic resonance spectroscopy and mass spectrometry (MS) in combination with gas chromatography-MS or liquid chromatography-MS. Metabolomics is used in many areas of medicine. The variability of biochemical processes in neoplastic cells in relation to healthy cells is the starting point for this type of research. The aim of the research currently being carried out is primarily to find biomarkers for quick diagnosis of the disease, assessment of its advancement and treatment effectiveness. The development of metabolomics may also contribute to the individualization of treatment of patients, adjusting drugs depending on the metabolic profile, and thus may improve the effectiveness of therapy, reduce side effects and help to improve the quality of life of patients. Here, we review the current and potential applications of metabolomics, focusing on its use as a biomarker method for childhood leukemia.

Structure and bioactivity of apple pectin isolated with arabinanase and mannanase.

It was assumed that, high purity endo-arabinanase and endo-mannanase could be useful in the isolation of pectin of enhanced health-promoting potential. Extraction was carried out with 50 U of enzymes per gram of apple pomace at 40 °C, obtaining up to 22% increase in effectiveness, as compared to the acid extraction. The pectins, despite their high Mw, were homogeneous and contained more galacturonic acid, rhamnose, galactose, fucose, and ferulic acid than the conventional product, thanks to which they quenched free radicals up to five times more efficiently. Compared with pectin with recognised anticancer and prebiotic activity, they had a significantly greater ability to inhibit proliferation and migration of HT-29 and B16F10 cells. They were also more effective in preventing the adhesion of E. coli and S. typhimurium to enterocytes. Endo-arabinanase- and endo-mannanase-assisted extraction is an effective method of obtaining pectins with enhanced antiradical, anticancer and prebiotic potential.

Application of selected biosensor techniques in clinical diagnostics.

INTRODUCTION: Examination of disease biomarkers mostly performed on crude materials, such as serum, meets some obstacles, resulting from sample complexity and the wide range of concentrations and sizes of the components. Techniques currently used in clinical diagnostics are usually time-consuming and expensive. The more sensitive and portable devices are needed for early diagnostics. Chemical sensors are devices that convert chemical information into parameters suitable for fast and precise processing and measurement. AREA COVERED: We review the use of biosensors and their possible application in early diagnostics of some diseases like cancer or viral infections. We focus on different types of biorecognition and some technical modifications, lowering the limit of detection potentially attractive to medical practitioners. EXPERT OPINION: Among the new diagnostic strategies, the use of biosensors is of increasing interest. In these techniques, the capture ligand interacts with the analyte of interest. Measuring interactions between partners in real time by surface plasmon resonance yields valuable information about kinetics and affinity in a short time and without labels. Importantly, the tendency in such techniques is to make biosensor devices smaller and the test results apparent with the naked eye, so they can be used in point-of-care medicine.

The intensity of physiological and behavioral responses of horses to predator vocalizations.

BACKGROUND: Predatory attacks on horses can become a problem in some parts of the world, particularly when considering the recovering gray wolf populations. The issue studied was whether horses transformed by humans and placed in stable-pasture environments had retained their natural abilities to respond to predation risk. The objective of the study was to determine the changes in cardiac activity, cortisol concentrations, and behavior of horses in response to the vocalizations of two predators: the gray wolf (Canis lupus), which the horses of the breed studied had coevolved with but not been exposed to recently, and Arabian leopard (Panthera pardus nimr), from which the horses had been mostly isolated. In addition, we hypothesized that a higher proportion of Thoroughbred (TB) horse ancestry in the pedigree would result in higher emotional excitability in response to predator vocalizations. Nineteen horses were divided into groups of 75%, 50% and 25% TB ancestry. The auditory test conducted in a paddock comprised a 10-min prestimulus period, a 5-min stimulus period when one of the predators was heard, and a 10-min poststimulus period without any experimental stimuli. RESULTS: The increase in heart rate and saliva cortisol concentration in response to predator vocalizations indicated some level of stress in the horses. The lowered beat-to-beat intervals revealed a decrease in parasympathetic nervous system activity. The behavioral responses were less distinct than the physiological changes. The responses were more pronounced with leopard vocalizations than wolf vocalizations. CONCLUSIONS: The horses responded with weak signs of anxiety when exposed to predator vocalizations. A tendency towards a stronger internal reaction to predators in horses with a higher proportion of TB genes suggested that the response intensity was partly innate. The more pronounced response to leopard than wolf may indicate that horses are more frightened of a threatening sound from an unknown predator than one known by their ancestors. The differing response can be also due to differences in the characteristic of the predators' vocalizations. Our findings suggested that the present-day horses' abilities to coexist with predators are weak. Hence, humans should protect horses against predation, especially when introducing them into seminatural locations.

TMPE Derived from Saffron Natural Monoterpene as Cytotoxic and Multidrug Resistance Reversing Agent in Colon Cancer Cells.

Terpenes constitute one of the largest groups of natural products. They exhibit a wide range of biological activities including antioxidant, anticancer, and drug resistance modulating properties. Saffron extract and its terpene constituents have been demonstrated to be cytotoxic against various types of cancer cells, including breast, liver, lung, pancreatic, and colorectal cancer. In the present work, we have studied anticancer properties of TMPE, a newly synthesized monoterpene derivative of ß-cyclocitral-the main volatile produced by the stigmas of unripe crocuses. TMPE presented selective cytotoxic activity to doxorubicin-resistant colon cancer cells and was identified to be an effective MDR modulator in doxorubicin-resistant cancer cells. Synergy between this derivative and doxorubicin was observed. Most probably, TMPE inhibited transport activity of ABCB1 protein without affecting its expression level. Analysis of TMPE physicochemical parameters suggested it was not likely to be transported by ABCB1. Molecular modeling showed TMPE being more reactive molecule than the parental compound-ß-cyclocitral. Analysis of electrostatic potential maps of both compounds prompted us to hypothesize that reduced reactivity as well as susceptibility to electrophilic attack were related to the lower general toxicity of ß-cyclocitral. All of the above pointed to TMPE as an interesting candidate molecule for MDR reversal in cancer cells.

Synthesis of nitrogen-containing monoterpenoids with antibacterial activity.

Incorporation of the Beckmann rearrangement into the presented research resulted in the formation of nitrogen-containing terpenoid derivatives originating from naturally occurring compounds. Both starting monoterpenes and obtained derivatives were subjected to estimation of their antibacterial potential. In the presented study, Staphylococcus aureus was the most sensitive to examined compounds. The Minimal Inhibitory Concentration (MIC) experiments performed on S. aureus demonstrated that the (-)-menthone oxime (-)-8 and (+)-pulegone oxime (+)-13 had the best antibacterial activity among the tested derivatives and starting compounds. Their MIC90 value was 100 µg/mL. The obtained derivatives were also evaluated for their inhibitory activity against bacterial urease. Among the tested compounds, three active inhibitors were found - oxime 14 and lactams (-)-15 and 16 limited the activity of Sporosarcina pasteurii urease with Ki values of 174.3 µM, 43.0 µM and 4.6 µM, respectively. To our knowledge, derivative 16 is the most active antiureolytic lactam described to date.

Synthesis and biological activity of new derivatives with the preserved carane system.

Terpenoid derivatives, which contain a preserved carane system in their structure, exhibit a broad spectrum of biological activities. Among them, we can distinguish insecticides, structures with pharmacological application etc. In the presented paper, the substrate - (-)-cis-caran-trans-4-ol was transformed using the reactions of typical organic synthesis to obtain novel derivatives. Most importantly, bromolactone ((-)-(1R,4R,6S)-2'-(bromomethyl)-4,7,7-trimethylspiro[bicyclo[4.1.0]heptan-3,3'-furan]-5'(4'H)-one) with the preserved carane system was synthesized. This bromolactone was tested for antifeedant activity against the lesser mealworm, Alphitobius diaperinus Panzer, and peach potato aphid (Myzus persicae). In addition, its moderate antibacterial activity was observed against the Bacillus subtilis strain (with Minimal Inhibitory Concentration of 200 µg/mL).

Synthesis and Biological Activity of New 4-tert-Butylcyclohexanone Derivatives.

In the synthesis performed in this study, derivatives of 4-tert-butylcyclohexanone 1 were obtained using typical reactions of organic synthesis. The bioactivity of the selected compounds was evaluated. 1-(Bromomethyl)-8-tert-butyl-2-oxaspiro[4.5]decan-3-one (5) was characterized by attractant properties against larvae and a weak feeding deterrent activity against adults of Alphitobius diaperinus Panzer. This bromolactone was a moderate antifeedant towards Myzus persicae Sulzer. In addition, ethyl (4-tert-butylcyclohexylidene)acetate (2) and bromolactone 5 displayed antibacterial activity. The strongest bacteriostatic effect was observed against Gram-positive strains: Bacillus subtilis and Staphylococcus aureus. The bromolactone 5 also limited the growth of Escherichia coli strain.

Synthesis of terpenoid oxo derivatives with antiureolytic activity.

Urease is an important virulence factor for a variety of pathogenic bacteria strains such as Helicobacter pylori, which colonizes human gastric mucosa, and Proteus sp., responsible for urinary tract infections. Specific inhibition of urease activity could be a promising adjuvant strategy for eradication of these pathogens. Due to the interesting antiureolytic activity of carvone and the scant information regarding the inhibitory properties of corresponding monoterpenes, we decided to study selected monoterpenic ketones and their oxygen derivatives. Several monoterpenes and their terpenoid oxygen derivatives were evaluated in vitro against Sporosarcina pasteurii urease. The most effective inhibitors-derivatives of ß-cyclocitral (ester 10 and bromolactone 14)-were described with [Formula: see text] of 46.7 µM and 45.8 µM, respectively. Active inhibitors of native urease were tested against H. pylori and Proteus mirabilis whole cells. Here, the most active inhibitor, 14, was characterized with IC50 values of 0.32 mM and 0.61 mM for P. mirabilis and H. pylori, respectively. The antibacterial activity of a few tested inhibitors was also observed. Compound 14 limited the growth of E. coli ([Formula: see text]= 250 µg/mL). Interestingly, 10 was the only compound that was effective against both Gram-negative and Gram-positive bacteria. It had a [Formula: see text] of 150 µg/mL against E. coli and S. aureus. In the presented study a group of novel antiureolytic compounds was characterised. Besides carvone stereoisomers, these are the only terpenoid urease inhibitors described so far.

An overview of the pharmacological properties and potential applications of natural monoterpenes.

Monoterpenes, the major components of essential oils, belong to the group of isoprenoids containing ten carbon atoms. Being widely distributed in the plant kingdom they are extensively used in cuisine and human health care products. Studies have shown that both natural monoterpenes and their synthetic derivatives are endowed with various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, antiarrhythmic, anti-aggregating, local anesthetic, antinociceptive, anti-inflammatory, antihistaminic and anti-spasmodic activities. Monoterpenes act also as regulators of growth, heat, transpiration, tumor inhibitors, inhibitors of oxidative phosphorylation, insect repellants, feline and canine attractants and antidiabetics. These interesting activities which might be potentially used not only in pharmaceutical, but also food and cosmetic industries are discussed below.