Low Molecular Weight Compounds Research Articles

Effect of changing the melanoidins by decoction on the release of volatiles in Zhenjiang aromatic vinegar

Melanoidins, making general contribution to the food characteristics, are extensively generated in the production of Chinese traditional vinegar; however, their effect on flavor modification remains unknown. This study investigated the changes in the melanoidins of Zhenjiang aromatic vinegar (ZAV) during decoction, and the interactions of crude melanoidins (CM) and pure melanoidins (PM) from decocted and undecocted ZAV with mixed aroma compounds were compared. With the exception of CN, OH and CH, chemical bonds and groups varied among the four types of melanoidins. However, CM and PM, obtained from decocted or undecocted vinegar, displayed generally similar structures, which resulted in their consistent retention of volatiles owning to the overall structure characteristics. Compared to aqueous solution, CM and PM from undecocted vinegar exhibited release, non-influence, or adsorption of flavors. However, melanoidins from decocted vinegar appeared the adsorption for all flavors but 2,3,5,6-Tetramethylpyrazine with weakened release. Free low molecular weight (LMw) compounds would affect the volatiles retention. Total solids (TS) from undecocted vinegar adsorbed volatiles except diethyl succinate; however, TS from decocted vinegar released all flavors significantly. Therefore, the decocted melanoidins were beneficial for the persistence of aroma. This study provided a base for elucidating the formation of melanoidins in decoction procedure and their roles in flavor modification.

TOPOLOGICAL CHARACTERISTICS OF THE STRUCTURE OF COMPOSITE MATERIALS

The article discusses methods for modeling composite materials using graph theory. For this purpose, the method of structure-oriented and structure-invariant modeling of composite materials was analyzed. As a basis for such modeling, it is supposed to use structural descriptors ‒ quantities that describe the structure of the material at different scale levels, including the molecular one. Structure-oriented modeling of hierarchical systems, which, in particular, are composite materials, can be carried out on the basis of regression statistical modeling, which takes into account the possibility of implementing the previous structural level at the next one, and, in particular, the molecular level at the microscopic or mesoscopic level. A form of experimental-statistical models, which includes descriptors of several structural levels was proposed. A simplified approach, which takes into account the regularities of two levels: molecular and subsequent (micro- and mesoscopic) was considered. Examples and algorithms for constructing a representative graph for cross-linked and branched polymers, as well as silicate materials, were considered. It is shown that the representing graph of cross-linked polymers is infinite stochastic. An experimental procedure for constructing a discrete model based on microphotographs of a hardening binder was considered and implemented. For a quantitative description of this graph, an incremental scheme was used, as well as topological indices obtained as a result of the transformation of topological indices of graphs of low molecular weight compounds. For the purpose of transformation, there is a transition to probabilistic characteristics ‒ shares and average (normalized) values. The transformed topological indices are supposed to be applied in the statistical model of the composite material.

Search for Ligands Complementary to the 430-cavity of Influenza Virus Neuraminidase by Virtual Screening

An anthrapyrazole derivative STK663786 has been identified as a selective ligand of the socalled 430-cavity of influenza virus neuraminidase at virtual screening of a library of low-molecularweight compounds. It is able to form favorable contacts with hydrophobic residues as well as cationπ interaction and hydrogen bonds with the polar Arg371 residue. The experimentally determined EC₅₀ values have been found to be 19 and 30 µM for viruses H1N1 and H3N2, respectively. Complementarity of STK663786 to the 430-cavity adjacent to the sialic acid binding subsite in the active center of neuraminidase makes this compound a valuable structural fragment at construction of bifunctional inhibitors of the enzyme.

LDI-MS performance of gold nanostars as an inorganic matrix for low molecular weight analytes

Anisotropy at the nanoscale fascinates researchers in various areas of science and technology. Well-known applications of anisotropic nanoparticles include biosensors and catalysis. However, utilization of gold nanostars in analytical chemistry is limited to surface enhanced Raman spectroscopy. LDI-MS assisted with gold nanostars has not been addressed for low molecular weight compounds. Herein, we report LDI-MS performance of phospholipids at nanomolar concentrations with application of gold nanostars for the first time. Intense signals of molecular ions were detected as metal adduct ions with relatively low fragmentation and signals of interferences in low-mass region. Nanostars were characterized with utilization of electron microscopic, X-Ray powder diffraction and dynamic light scattering techniques. The results showed that gold nanostars can serve as a bright perspective for new inorganic matrices in LDI-MS of low molecular weight compounds.

Process Optimization and Stability of Waste Orange Peel Polyphenols in Extracts Obtained with Organosolv Thermal Treatment Using Glycerol-Based Solvents

This study was focused on the simultaneous organosolv treatment/extraction of waste orange peels (WOP) for the effective recovery of polyphenolic antioxidants. The treatments were performed with aqueous glycerol mixtures, which were acidified either with citric acid or hydrochloric acid (HCl). Process optimization was carried out using response surface methodology and comparative appraisal of the different processes tested, based on both the extraction efficiency factor (FEE), severity factor (SF) or combined severity factor (CSF). Metabolite stability was also of major concern, and it was examined by deploying liquid chromatography-mass spectrometry. The results drawn suggested 90% (w/w) glycerol to be the highest-performing system, providing a yield in total polyphenols of 44.09 ± 5.46 mg GAE g−1 DM at 140 °C for 50 min, with a FEE of 2.20 and an SF of 2.88. Acidification with 1% citric acid was proven less efficient and equally severe, whereas acidification with 1% HCl was less severe but also less efficient. The major disadvantage associated with the use of HCl was its detrimental impact on the polyphenolic composition of WOP since major metabolites, such as narirutin, hesperidin and didymin, did not survive the process. By contrast, the formation of lower molecular weight compounds was observed. With regard to antioxidant properties, the extract obtained with aqueous glycerol displayed significantly higher antiradical activity and reducing power, which was in line with its higher concentration in total polyphenols. It was concluded that organosolv treatment with aqueous glycerol under the conditions employed may boost polyphenol recovery from WOP, thus giving extracts with powerful antioxidant characteristics.

Amorphization of Drugs for Transdermal Delivery-a Recent Update.

Amorphous solid dispersion is a popular formulation approach for orally administered poorly water-soluble drugs, especially for BCS class II. But oral delivery could not be an automatic choice for some drugs with high first-pass metabolism susceptibility. In such cases, transdermal delivery is considered an alternative if the drug is potent and the dose is less than 10 mg. Amorphization of drugs causes supersaturation and enhances the thermodynamic activity of the drugs. Hence, drug transport through the skin could be improved. The stabilization of amorphous system is a persistent challenge that restricts its application. A polymeric system, where amorphous drug is dispersed in a polymeric carrier, helps its stability. However, high excipient load often becomes problematic for the polymeric amorphous system. Coamorphous formulation is another approach, where one drug is mixed with another drug or low molecular weight compound, which stabilizes each other, restricts crystallization, and maintains a single-phase homogenous amorphous system. Prevention of recrystallization along with enhanced skin permeation has been observed by the transdermal coamorphous system. But scalable manufacturing methods, extensive stability study and in-depth in vivo evaluation are lacking. This review has critically studied the mechanistic aspects of amorphization and transdermal permeation by analyzing recent researches in this field to propose a future direction.

RXFP2 Small Molecule Agonists: Potential Therapeutics for Osteoporosis

Osteoporosis is a chronic bone disease characterized by decreased bone mass and increased risk of developing fractures, predominantly observed in the elderly. Osteoporosis affects approximately 10 million people in the US, and the number is expected to increase exponentially as the elderly population continues to grow. The pathophysiological cause of the disease is a decrease in the activity of the bone‐forming cells (osteoblasts) that alters bone remodeling in favor of bone resorption, leading to a decrease in bone mass. Recent studies identified the G protein‐coupled receptor (GPCR) for insulin‐like 3 peptide (INSL3), relaxin family peptide receptor 2 (RXFP2), as an attractive target for the treatment of osteoporosis. The goal of this study is to develop small molecule agonists of RXFP2, expressed in osteoblast cells, to promote bone growth and counteract the deleterious effects of osteoporosis. Currently, the most effective available treatment for osteoporosis is an expensive hormone therapy that requires daily injections. We aim to create drugs that are stable and can be delivered orally. Several low molecular weight compounds were identified as agonists of the RXFP2 receptor using a high‐throughput screen of the NCATS small molecule library. The screening assay measured cAMP response in RXFP2‐transfected HEK293T cells. An extensive structure‐activity relationship campaign resulted in highly potent and efficient full RXFP2 agonists. The selectivity and specificity of the compounds for human and mouse RXFP2 was shown using orthogonal cAMP assays, counter‐screening against the related relaxin receptor RXFP1, and a GPCRome screen using the PRESTO‐Tango assay. The drug candidates were further tested in primary human osteoblasts to demonstrate that they promote mineralization by measuring hydroxyapatite deposition in the cell matrix. We showed that the compounds had low cytotoxicity in various cell types. Using a series of RXFP2/RXFP1 chimeric receptors, we established that the compounds are allosteric agonists of the RXFP2 receptor and identified the GPCR transmembrane domains as the specific region for compound interaction. The RXFP2 agonist with the highest activity in vitro was selected for pharmacokinetics (PK) profiling in mice, showing optimal oral bioavailability and bone exposure. An efficacy study using 2‐month‐old WT female mice treated orally with 10 mg/kg of compound 3 times a week for 8 weeks showed a significant increase of the vertebral trabecular number and thickness by micro‐CT analysis compared to vehicle treated controls. We expect that the further characterization of these compounds may lead to the development of a new class of cost‐effective drugs for the treatment of osteoporosis and other diseases associated with bone loss.

Adsorption Isotherms of Dimethyl Phthalate (DMP), DiEthyl Phthalate (DEP), Dibutyl Phthlate (DBP) and Benzyl Butyl Phthalate (BBP) Compounds in Synthetic and Sembrong River Sediment

Concentrations of Dimethyl Phthalate (DMP), Diethyl Phthalate (DEP), Dibutyl Phthlate (DBP), and Benzyl Butyl Phthalate (BBP) analysis proved present in Sembrong river sediment. These findings occurred during a certain extent of time depending on the properties of sediment and phthalates esters compound. Therefore, adsorption isotherm conducted using optimization method using manipulating variables of initial concentrations and contact times. The results analysis showed higher percentage adsorption recorded in DMP, DEP, DBP and BBP compounds by synthetic sediment which is 88.3%,89.6%,89.0% and 94.8% whereas river sediment is 87.4%,88.4%, 87.1% and 93.4%. The contributing factors aided in the adsorption of PAEs onto synthetic sediment are higher organic content (OC), smaller particle size having larger surface area and higher molecular weight of PAEs. Competitive adsorption occurred between DMP, DEP and DBP as they are low molecular weight compounds. Adsorption isotherms models by Langmuir and Freundlich isotherms models showed separation factor, RL values are favourable from 0.11 to 0.69. Good statistical fit R2 ranged from 0.97 to 0.99 of a good fit. Therefore, in conclusion, Sembrong river sediment is an adsorbent sediment storage of PAEs compounds.

Co3O4 nanocrystals as matrices for the detection of amino acids, harmful additives and pesticide residues by MALDI-TOF MS.

Research of detection of low molecular weight compounds on human health and biological systems become increasingly important. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), a soft ionization equipment, is a rapid, reliable, high-sensitivity, high-throughput and simple test instrument. However, the application of MALDI-TOF MS in the analysis of small molecules (<500Da) has become a great challenge because of the interference from the conventional matrices in low mass region when using conventional matrices. In this research, tricobalt tetraoxide (Co3O4) nanocrystals with rich surface hydroxyl groups were synthesized and served as novel matrices for the detection of small molecules by MALDI-TOF MS. In comparison with conventional organic matrices, the use of as-prepared Co3O4 nanocrystal matrices showed little matrix background interference, good reproducibility and high signal intensity in the analyses of amino acids, harmful additives and pesticide residues. For the detection of most amino acids, Co3O4 nanocrystal matrices have good detection performance both in the positive and negative ion modes and have a unique decarboxylation peak in the positive ion mode, which is conducive to the identification of amino acids. In addition, Co3O4 nanocrystals are completely feasible to test triadimefon, pirimicarb and other pesticide residues, as well as additives such as bisphenol A and melamine in the positive ion mode. It is also feasible to detect small molecule compounds in practical samples using Co3O4 nanocrystals as matrices. We believe the work provides an alternative approach for the detection of small molecules and expands the application scope of Co3O4 nanocrystals.

Single-Walled Carbon Nanohorns as Boosting Surface for the Analysis of Low-Molecular-Weight Compounds by SALDI-MS.

Limits of Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry (MS) in the study of small molecules are due to matrix-related interfering species in the low m/z range. Single-walled carbon nanohorns (SWCNH) were here evaluated as a specific surface for the rapid analysis of amino acids and lipids by Surface-Assisted Laser Desorption Ionization (SALDI). The method was optimized for detecting twenty amino acids, mainly present as cationized species, with the [M+K]+ response generally 2-time larger than the [M+Na]+ one. The [M+Na]+/[M+K]+ signals ratio was tentatively correlated with the molecular weight, dipole moment and binding affinity, to describe the amino acids’ coordination ability. The SWCNH-based surface was also tested for analyzing triglycerides in olive oil samples, showing promising results in determining the percentage composition of fatty acids without any sample treatment. Results indicated that SWCNH is a promising substrate for the SALDI-MS analysis of low molecular weight compounds with different polarities, enlarging the analytical platforms for MALDI applications.

Inorganic Salt Catalysed Hydrothermal Carbonisation (HTC) of Cellulose

The presence of inorganic salts either as part of the substrate or added to the reaction medium are known to significantly affect the reaction pathways during hydrothermal carbonisation (HTC) of biomass. This work aims to understand the influence of salts on hydrothermal carbonisation by processing cellulose in the presence of one or more inorganic salts with different valency. Batch experiments and Differential Scanning Calorimetry were used to investigate the change in reaction pathways during hydrothermal conversion. The effect of salts on the rate of HTC of cellulose can be correlated with the Lewis acidity of the cation and the basicity of the anion. The effect of the anion was more pH-dependent than the cation because it can protonate during the HTC process as organic acids are produced. The introduction of salts with Lewis acidity increases the concentration of low molecular weight compounds in the process water. The addition of a second salt can influence the catalytic effect of the first salt resulting in greater levulinic acid yields at the expense of hydrochar formation. Salts also play an important role in cellulose dissolution and can be used to modify the yield and composition of the hydrochars.

Risk of developing drug abuse in administration of a new hexaazaisowurtzitane derivative-based analgesic (experimental study)

The aim of the study was to assess the probability of developing withdrawal syndrome caused by discontinuation of 5-day administration of thiowurtzine with naloxone challenge test in the experiment.Materials and methods. The test sample of the analgesic “Thiowurtzine, capsule 120 mg” served as the study object. The active pharmaceutical ingredient is an organic, low molecular weight compound 4-(3,4-dibromothiophene carbonyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo [5,5,0,03,11,05,9]dodecane that was first synthesized according to computer modeling results at the IPCET SB RAS (Biysk).The likelihood of developing physical dependence was explored by per os administration of thiowurtzine and the reference drug tramadol twice a day for 5 days as follows: 1) at 9 a.m. – thiowurtzine 50 mg / kg and tramadol 10 mg / kg, at 3 p.m. – thiowurtzine 50 mg / kg and tramadol 10 mg / kg; 2) at 9 a.m. – thiowurtzine 50 mg / kg and tramadol 10 mg / kg, at 3 p.m. – thiowurtzine 75 mg / kg and tramadol 15 mg / kg; 3) at 9 a.m. – thiowurtzine 75 mg / kg and tramadol 15 mg / kg, at 3 p.m. – thiowurtzine 75 mg / kg and tramadol 15 mg / kg; 4) at 9 a.m. – thiowurtzine 100 mg / kg and tramadol 20 mg / kg, at 3 p.m. – thiowurtzine 100 mg / kg and tramadol 20 mg / kg; 5) at 9 a.m. – thiowurtzine 100 mg / kg and tramadol 20 mg / kg, at 3 p.m. – naloxone 10 mg / kg subcutaneously.In all the groups, the intensity of the withdrawal syndrome was studied by specific features in outbred male CD1 mice. During one hour following the naloxone injection, health of mice was assessed according to dominant abstinence components and recessive traits of mild withdrawal syndrome. Two hours after the naloxone injection, the number of mice with negative body weight gain was determined. 24 hours after discontinuation of test compound administration, the open-field test was used to determine the impact on animal behavioral patterns (horizontal and vertical motor and exploratory activity, emotionality and its vegetative manifestations). The hot plate test was carried out to measure the analgesic activity (55˚). The criterion of the withdrawal syndrome severity was a decrease in the number of jumping reactions, changes in the general condition of the animals, stimulation of motor activity, manifestations of hyperalgesia, and a decrease in body weight.Results. No dominant abstinence components and recessive signs of withdrawal syndrome were detected in animals from the thiowurtzine groups. The data obtained in the study (orientation and exploratory behavior, motor activity, emotionality and its vegetative manifestations, grooming, etc.) allow to conclude that thiowurtzine causes no physical dependence in animals after discontinuation of its 5-day administration with naloxone challenge test, as opposed to the reference drug naloxone. A positive disinhibition effect of this analgesic was revealed due to the activated orientation and exploratory behavior (stress caused by the new environment) in the conditions of the open-field test. The animals showed no manifestations of hyperalgesia in the hot plate test. The animals treated with thiowurtzine did not demonstrate any changes in the body weight.Conclusion. The obtained results prove that thiowurtzine is a non-narcotic analgesic. It evokes no side effects typical of opioid analgesics (tramadol), including development of physical dependence and withdrawal syndrome following naloxone challenge test. Previous in vivo and in silico studies (docking, molecular modeling, molecular dynamics simulation) on the multi-target mechanism of thiowurtzine explain the absence of its morphine-like effect by the fact that the major targets of the analgesic are TRPA1 receptors and voltage-gated Ca 2+ channels. With a high degree of probability, the conclusions made herein predict no drug abuse development when thiowurtzine is used in the clinical setting. Absence of ulcerotoxicity found earlier will enable to administer thiowurtzine in long-term cycles for chronic pain syndrome.

Exploration of key aroma active compounds in strong flavor Baijiu during the distillation by modern instrument detection technology combined with multivariate statistical analysis methods

Liquid-liquid microextraction (LLME) combined with gas chromatography-mass spectrometry (GC-MS) and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were used to detect the variations in volatile compounds during the distillation process of strong flavor raw Baijiu. The 3D fingerprint spectrum clearly showed a variation in volatile compounds from different distillation stages, and most alcohol-soluble and low molecular weight compounds showed a downward trend with the extension of distillation time, but water-soluble, high molecular weight and high boiling compounds showed the opposite result. Then, 50 aroma compounds were sniffed and identified by gas chromatography-olfactometry-mass spectrometry (GC-O-MS) and multivariate statistical analysis including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) confirmed four aroma active markers related to classification. Finally, the receiver operating characteristic (ROC) curve was further used to verify that ethyl butanoate and ethyl hexanoate were the most effective difference marker to distinguish the head Baijiu samples and butanoic acid was the most effective difference marker for distinguishing the heart Baijiu samples from the tail Baijiu samples.

Tunable polymorphic crystal modification, phase transition and biodegradability of poly(1,4-butylene adipate) by a bio-derived metabolite with low molecular weight

Via the H-bond interaction, the 3,4-dihydroxy hydrocinnamic acid (HCA, a low molecular weight compound with biocompatibility) decreased the melt-crystallization temperature (Tc), crystallization rate and relative degree of the crystallinity of the poly(1,4-butylene adipte) (PBA) polyester. In the case of the lower weight fraction of the HCA (fHCA = 1-5%), the H-bond exists between the -CH2 segment of the HCA and -C=O group of the PBA. When fHCA = 10-30%, there is a larger H-bond strength between the HCA and PBA, and the -C=O segment of the HCA interacts with the -CH2 segment of the PBA. The HCA facilitated the generation of the PBA alpha-modification at a lower Tc and accelerated the transition from the beta- to alpha-phase. The polymorphism and phase transition of the PBA could be tuned by the HCA. Lower fHCA enhanced slightly the thermal degradation temperature (Td), but higher fHCA decreased the Td of the PBA. The HCA increased the biodegradability of the PBA. Mechanisms on reduced critical Tc of the PBA alpha-modification (Tc,α), speeded up phase transition, enhanced biodegradability and dual effects of the HCA on the thermal stability of the PBA, were also proposed and discussed systematically and in depth.

A Sea Anemone Lebrunia neglecta Venom Fraction Decreases Boar Sperm Cells Capacitation: Possible Involvement of HVA Calcium Channels.

Sea anemones produce venoms characterized by a complex mixture of low molecular weight compounds, proteins and peptides acting on voltage-gated ion channels. Mammal sperm cells, like neurons, are characterized by their ion channels. Calcium channels seem to be implicated in pivotal roles such as motility and capacitation. In this study, we evaluated the effect of a low molecular weight fraction from the venom of the sea anemone Lebrunia neglecta on boar sperm cells and in HVA calcium channels from rat chromaffin cells. Spermatozoa viability seemed unaffected by the fraction whereas motility and sperm capacitation were notoriously impaired. The sea anemone fraction inhibited the HVA calcium current with partial recovery and no changes in chromaffin cells’ current kinetics and current–voltage relationship. These findings might be relevant to the pharmacological characterization of cnidarian venoms and toxins on voltage-gated calcium channels.

Nitrogen increases early‐stage and slows late‐stage decomposition across diverse grasslands

Abstract To evaluate how increased anthropogenic nutrient inputs alter carbon cycling in grasslands, we conducted a litter decomposition study across 20 temperate grasslands on three continents within the Nutrient Network, a globally distributed nutrient enrichment experiment We determined the effects of addition of experimental nitrogen (N), phosphorus (P) and potassium plus micronutrient (Kμ) on decomposition of a common tree leaf litter in a long‐term study (maximum of 7 years; exact deployment period varied across sites). The use of higher order decomposition models allowed us to distinguish between the effects of nutrients on early‐ versus late‐stage decomposition. Across continents, the addition of N (but not other nutrients) accelerated early‐stage decomposition and slowed late‐stage decomposition, increasing the slowly decomposing fraction by 28% and the overall litter mean residence time by 58%. Synthesis. Using a novel, long‐term cross‐site experiment, we found widespread evidence that N enhances the early stages of above‐ground plant litter decomposition across diverse and widespread temperate grassland sites but slows late‐stage decomposition. These findings were corroborated by fitting the data to multiple decomposition models and have implications for N effects on soil organic matter formation. For example, following N enrichment, increased microbial processing of litter substrates early in decomposition could promote the production and transfer of low molecular weight compounds to soils and potentially enhance the stabilization of mineral‐associated organic matter. By contrast, by slowing late‐stage decomposition, N enrichment could promote particulate organic matter (POM) accumulation. Such hypotheses deserve further testing.

Mapping of FSHR agonists and antagonists binding sites to identify potential peptidomimetic modulators.

Owing to the critical role of follicle stimulating hormone receptor (FSHR) signaling in human reproduction, FSHR has been widely explored for development of fertility regulators. Using high-throughput screening approaches, several low molecular weight (LMW) compounds that can modulate FSHR activity have been identified. However, the information about the binding sites of these molecules on FSHR is not known. In the present study, we extracted the structural and functional information of 161 experimentally validated LMW FSHR modulators available in PubMed records. The potential FSHR binding sites for these modulators were identified through molecular docking experiments. The binding sites were further mapped to the agonist or antagonist activity reported for these molecules in literature. MD simulations were performed to evaluate the effect of ligand binding on conformational changes in the receptor, specifically the transmembrane domain. A peptidomimetic library was screened using these binding sites. Six peptidomimetics that interacted with the residues of transmembrane domain and extracellular loops were evaluated for binding activity using in vitro cAMP assay. Two of the six peptidomimetics exhibited positive allosteric modulatory activity and four peptidomimetics exhibited negative allosteric modulatory activity. All six peptidomimetics interacted with Asp521 of hFSHR(TMD). Several of the experimentally known LMW FSHR modulators also participated in H-bond interactions with Asp521, suggesting its important role in FSHR modulatory activity.

The Influence of Chlorpyrifos on the Nonenzymatic Antioxidants Content in Macrophytes Leaves.

Water pollution can be moved or limited by macrophytes in a phytoremediation process. The presence of insecticides in the plant life environment may affect physiological processes and contribute to the formation of secondary oxidative stress in plant tissues. To protect against oxidative stress, macrophytes have developed a system of mechanisms consisting of nonenzymatic and enzymatic antioxidants. The influence of various concentrations of chlorpyrifos on the nonenzymatic system in Canadian waterweed (Elodea canadensis Michx.), needle spikerush (Eleocharis acicularis) and water mint (Mentha aquatica L.) was studied. The differences in the value of the total concentration of polyphenols and flavonoids, as well as analysis of chlorophyll-a, chlorophyll-b, anthocyanin and carotenoid concentrations were determined in leaves. Research indicated a significant increase in the content of polyphenols and flavonoids in a solution with the highest concentration of chlorpyrifos while the opposite tendency was observed after analyses of the main assimilating pigments of plant tissues. It was concluded that aqueous plants exposed to toxic insecticide molecules created a defensive mechanism by nonenzymatic antioxidant systems and the amount of low-molecular weight compounds depended on the pollutant concentration which influenced biosynthesis mechanisms in plant cells.

Экскреция триптофана, лизина, триметиллизина, саркозина, холина и 4-пиридоксиновой кислоты с мочой при мочекаменной болезни

Introduction. The role of the organic matrix in urinary stones genesis in urolithiasis patients is still unclear. The presence of a large amount of protein in the urinary stones matrix suggests the participation of the protein matrix in lithogenesis. Research of the amino acids spectrum in urine is of great interest so far as amino acids are the part of the matrix proteins of the urinary stone. Material and methods. We analyzed urinary excretion of the following amino acids and low molecular weight compounds: tryptophan, lysine, trimethyllysine, sarcosine, choline and 4-pyridoxine acid. We used ultra-performance liquid chromatography in combination with a TQD mass spectrometer. Results. A higher level of excretion of choline and sarcosine is typical for patients with oxalate stones, compared with healthy people. Uric acid stone patients have high concentration of choline and extremely increased concentration of trimethyllysine in the urine unlike healthy individuals. Very low concentration of trimethyllysine, choline, sarcosine and higher excretion of tryptophan are specific for oxalate urolithiasis, in contrast to urate stone patients. Conclusion. The intensity of amino acids and low molecular weight compounds urinary excretion has characteristic features in patients with various types of urolithiasis and healthy individuals. Indicators of excretion of these amino acids and low molecular weight substances can serve as criteria for the activity of oxalate or urate lithogenesis along with the known metabolic lithogenic factors of urine. We can use it as additional target indicators to assess the success of anti-relapse treatment.

STING Agonists/Antagonists: Their Potential as Therapeutics and Future Developments.

The cGAS STING pathway has received much attention in recent years, and it has been recognized as an important component of the innate immune response. Since the discovery of STING and that of cGAS, many observations based on preclinical models suggest that the faulty regulation of this pathway is involved in many type I IFN autoinflammatory disorders. Evidence has been accumulating that cGAS/STING might play an important role in pathologies beyond classical immune diseases, as in, for example, cardiac failure. Human genetic mutations that result in the activation of STING or that affect the activity of cGAS have been demonstrated as the drivers of rare interferonopathies affecting young children and young adults. Nevertheless, no data is available in the clinics demonstrating the therapeutic benefit in modulating the cGAS/STING pathway. This is due to the lack of STING/cGAS-specific low molecular weight modulators that would be qualified for clinical exploration. The early hopes to learn from STING agonists, which have reached the clinics in recent years for selected oncology indications, have not yet materialized since the initial trials are progressing very slowly. In addition, transforming STING agonists into potent selective antagonists has turned out to be more challenging than expected. Nevertheless, there has been progress in identifying novel low molecular weight compounds, in some cases with unexpected mode of action, that might soon move to clinical trials. This study gives an overview of some of the potential indications that might profit from modulation of the cGAS/STING pathway and a short overview of the efforts in identifying STING modulators (agonists and antagonists) suitable for clinical research and describing their potential as a “drug”.