Hasil untuk "Organic chemistry"

Helena Torpy, The Huong Chau, Sayantani Chatterjee et al.

The morbidity and mortality of sepsis remain high. Clinicians lack effective markers to rapidly diagnose sepsis and identify the underlying pathogen infection particularly for patients with candidaemia or cases of culture-negative sepsis where culture-based diagnostics are inadequate. In our search for new lines of potential sepsis biomarkers, we here explore the impact of various classes of infectious agents on the serum N-glycome in a septic shock cohort. Comparative N-glycomics was performed on sera collected from 49 septic shock patients infected with viral (n = 9), bacterial (n = 37) or fungal (n = 3) pathogens using an established PGC-LC-MS/MS method. Aberrant serum N-glycosylation features were observed in patients with fungal infection relative to the other infection sub-groups including i) altered expression of prominent α2,6-sialylated biantennary N-glycan isomers, ii) elevated levels of IgG-type N-glycosylation and iii) a global shift in the serum N-glycome involving altered glycan type distribution and considerable changes in core fucosylation and α2,6-sialylation. Septic shock patients infected with bacterial and viral pathogens exhibited similar global serum N-glycome features and therefore could not be stratified based on their serum N-glycosylation. Subtle and less consistent serum N-glycome differences were observed between septic shock patients infected with different bacterial pathogens. In conclusion, our study has tested the impact of different pathogen classes on the serum N-glycome in a septic shock cohort, and reports that fungal infection impacts the host serum N-glycome differently compared to bacterial or viral infections thus potentially opening avenues for glycan-based biomarkers to better diagnose patients with candidaemia.

Paola Sist, Ranieri Urbani, Federica Tramer et al.

HUG is the HELP-UnaG recombinant fusion protein featuring the typical functions of both HELP and UnaG. In HUG, the HELP domain is a thermoresponsive human elastin-like polypeptide. It forms a shield enwrapping the UnaG domain that emits bilirubin-dependent fluorescence. Here, we recapitulate the technological development of this bifunctional synthetic protein from the theoretical background of its distinct protein moieties to the detailed characterization of its macromolecular and functional properties. These pieces of knowledge are the foundations for HUG production and application in the fluorometric analysis of bilirubin and its congeners, biliverdin and bilirubin glucuronide. These bile pigments are metabolites that arise from the catabolism of heme, the prosthetic group of cytochromes, hemoglobin and several other intracellular enzymes engaged in electron transfer, oxygen transport and protection against oxygen free radicals. The HUG assay is a powerful, user-friendly and affordable analytical tool that alone supports research at each level of complexity or taxonomy of living entities, from enzymology, cell biology and pathophysiology to veterinary and clinical sciences.

Shaozhou Zhu, Yan Liu, Hang Wang et al.

Advances in whole genome sequencing have transformed GenBank into a veritable goldmine of uncharacterized and predicted proteins, many of which still await functional characterization. Notably, natural product biosynthetic pathways are often organized in gene clusters, unlocking thrilling avenues for the discovery of novel metabolites and distinctive enzymatic reactions. In this review, we focus on the versatile ThiF-like adenylyltransferase superfamily (TLATs), a group of enzymes essential for the biosynthesis of a diverse array of ribosomally synthesized and post-translationally modified peptides (RiPPs). Recent researches have revealed that TLATs are widespread in numerous yet uncharacterized RiPP biosynthetic pathways, highlighting significant gaps in our understanding of their extensive catalytic potential. Here, we critically review the latest insights into RiPP gene clusters containing these enzymes, discussing the natural products they generate, their enzymatic functions, catalytic mechanisms, and promising directions for future research.

Rimsha Khan, Saima Anjum, Nishat Fatima et al.

Neurotransmitters are essential chemical messengers required for proper brain function, and any changes in their concentrations can lead to neuronal diseases. Therefore, sensitive and selective detection is crucial. This study presents a fast and simple colorimetric method for dopamine detection using three reagent solutions: AgNP and MPA, Ag/Au nanocomposite, and mercaptophenylacetic acid. TEM images showed a narrow distribution of Ag and Au nanoparticles with average sizes of 20 nm and 13 nm, respectively, with gold nanoparticles bound to the edges of silver nanoparticles. A paper-based biosensor was created using manual wax printing for the colorimetric detection of dopamine. Visual detection onsite showed color changes with both the silver nanoparticles and mercaptophenylacetic acid mixture and the silver–gold nanoparticle composite. Electrochemical detection using a glassy carbon electrode modified with 8 mM mercaptophenylacetic acid demonstrated high selectivity and sensitivity towards dopamine, with a peak in the range of 0.7–0.9 V. Interferences were minimized, ensuring high sensitivity and selective detection of dopamine.

Karolina Ptaszyńska, Anna Malaika, Katarzyna Morawa Eblagon et al.

A facile and eco-friendly approach using in situ-generated 4-benzenediazonium sulfonate (BDS) was applied to prepare highly functionalized carbon nanotubes (CNTs). The effectiveness of this functionalization was additionally enhanced by a green and short-time ball milling process applied beforehand. The obtained BDS-modified CNTs presented significant activity in glycerol etherification, producing tert-butyl glycerol ethers, which are considered promising fuel additives. Excellent results of ~56% glycerol conversion and ~10% yield of higher-substituted tert-butyl glycerol ethers were obtained within just 1 h of reaction at 120 °C using a low catalyst loading of only 2.5 wt.%. Furthermore, the sulfonated CNTs were reusable over several reaction cycles, with only a minor decrease in activity. Additionally, the sample activity could be restored by a simple regeneration approach. Finally, a clear correlation was found between the content of -SO₃H groups on the surface of CNTs and the catalytic performances of these materials in glycerol etherification. Improved interaction between functionalized ball-milled CNTs and the reactants was also suggested to positively affect the activity of these catalysts in the tested process.

Bertrand Lefeuvre, Thierry Guizouarn, Vincent Dorcet et al.

The reaction between the ((<i>E</i>)-<i>N</i>′-(2-hydroxy-3-methoxybenzylidene)pyrazine-2-carbohydrazide) (H₂opch) ligand and the metallo-precursor [Dy(hfac)₃]·2H₂O led to the formation of an homometallic coordination complex with the formula [Dy₂(hfac)₃(H₂O)(Hopch)₂][Dy(hfac)₄] (<b>1</b>). In presence of both [Dy(hfac)₃] 2H₂O and the Fe(II) salt, the heterobimetallic tetranuclear [FeDy₃(hfac)₈(H₂O)₂(opch)₂] (<b>2</b>) was isolated, while the addition of the co-ligand 1,2-Bis(2-hydroxy-3-methoxybenzylidene) hydrazine (H₂bmh) led to the formation of two heterobimetallic tetranuclear complexes with the formula [Fe₃Dy(hfac)₆(opch)₂(H₂bmh)] C₆H₁₄ (<b>3</b>) <b>C₆H₁₄</b> and [Fe₂Dy₂(hfac)₇(opch)₂(H₂bmh)] 0.5C₇H₁₆ (<b>4</b>) <b>0.5C₇H₁₆</b>. Single crystal X-ray diffraction and dc magnetic investigation demonstrated that <b>3</b> and <b>4</b> involved the iron center in the +II and +III oxidation states. Dynamic magnetic measurements highlighted the single-molecule magnet behavior of <b>1</b> and <b>2</b> in a zero applied dc field primarily due to the ferromagnetic interactions taking place in these compounds.

Yulistiani Yulistiani, Surya Dwiyatna, Febriansyah Nur Utomo

Autoimmune hemolytic anemia (AIHA) is a rare condition in which autoantibodies cause the loss of red blood cells. Steroids have been used to treat several illnesses, including AIHA. For now, steroids remain as the first line of treatment for AIHA. In AIHA, especially warm AIHA (wAIHA), steroids suppress autoantibody production and downregulate Fcγ receptors' expression on monocytes to prevent hemolysis. The type of steroids chosen for first-line therapy for wAIHA in pediatrics and adults are Prednisone (Prednisolone) and Methylprednisolone. At the same time, Dexamethasone is used as an alternative treatment in AIHA. Steroids show better therapeutic outcomes in the first 2-3 weeks of administration, but the proportion of patients who remain in remission after steroid discontinuation are still quite low. Long-term administration of steroids may affect bone, blood glucose metabolism, and hypothalamic-pituitary-adrenal axis (HPAA). However, steroids which have a linear pharmacokinetic profile, intermediate-acting glucocorticoids such as Prednisone (Prednisolone) or Methylprednisolone, and also tapering dose of steroids after 2-4 weeks administration will be safe for long term use as AIHA treatment. Keywords: steroids, glucocorticoid, corticosteroid, autoimmune hemolytic anemia, AIHA, mechanism of action, efficacy

Lorenzo Carli, Anyawan Tapdara, Jianwen Jin et al.

A synthetic method for the preparation of 1,8-dihydroindeno[2,1-b]pyrroles and pyrrol-2-yl methanols in an enantioselective manner that relies on the chiral gold(I)-catalysed reactions of β-amino-1,4-enynols is described. A divergence in product selectivity was achieved by exploiting the electrostatic interactions between the chiral counteranion of the metal catalyst and the substrate. With a gold(I) complex containing a chiral N-triflyl phosphoramide-based counteranion, tandem dehydrative Nazarov-type electrocyclisation/hydroamination of the substrate was found to selectively occur to afford the indeno-fused pyrrole adduct. In contrast, changing to a chiral phosphate-based counteranion was observed to result in a hydroamination/enantioselective formal 1,3-allylic alcohol isomerisation cascade pathway to give the 1H-pyrrole derivative.

Yenice Sedef

The increasing availability and use of POCT are influenced by many factors, including the industry trend toward patient-centered care and decentralization of health care; the increasing prevalence of infectious diseases, which includes the current use of rapid SARS-CoV-2 testing; the increasing incidence of lifestyle diseases such as diabetes, heart disease, and hypertension; and advances in in-vitro medical diagnostics. The use of POCT can increase the efficiency of services and improve patient outcomes. However, the variability of the testing environment and conditions, as well as the competency of the staff performing the tests, can have a significant impact on the quality and accuracy of POCT results. Most personnel performing POCT are not trained laboratory staff and may not be as familiar with the processes associated with testing, such as patient preparation, specimen collection, management of equipment and supplies, calibration and maintenance of equipment, the performance of the test, quality control, interpretation of results, and reporting/documentation of results related to the particular patient. Therefore, personnel performing POCT must have the appropriate training and experience to ensure that test results are accurate and reliable. This review outlines the specific personnel training requirements based on international standards that must be considered to ensure the quality of test results and describe the competency criteria required for POCT compliance.

Diana I. S. P. Resende, Joana R. Almeida, Sandra Pereira et al.

Biofouling, which occurs when certain marine species attach and accumulate in artificial submerged structures, represents a serious economic and environmental issue worldwide. The discovery of new non-toxic and eco-friendly antifouling systems to control or prevent biofouling is, therefore, a practical and urgent need. In this work, the antifouling activity of a series of 24 xanthones, with chemical similarities to natural products, was exploited. Nine (<b>1</b>, <b>2</b>, <b>4</b>, <b>6</b>, <b>8</b>, <b>16</b>, <b>19</b>, <b>21</b>, and <b>23</b>) of the tested xanthones presented highly significant anti-settlement responses at 50 μM against the settlement of mussel <i>Mytilus galloprovincialis</i> larvae and low toxicity to this macrofouling species. Xanthones <b>21</b> and <b>23</b> emerged as the most effective larval settlement inhibitors (EC₅₀ = 7.28 and 3.57 µM, respectively). Additionally, xanthone <b>23</b> exhibited a therapeutic ratio (LC₅₀/EC₅₀) > 15, as required by the US Navy program attesting its suitability as natural antifouling agents. From the nine tested xanthones, none of the compounds were found to significantly inhibit the growth of the marine biofilm-forming bacterial strains tested. Xanthones <b>4</b>, <b>6</b>, <b>8</b>, <b>16</b>, <b>19</b>, <b>21</b>, and <b>23</b> were found to be non-toxic to the marine non-target species <i>Artemia salina</i> (<10% mortality at 50 μM). Insights on the antifouling mode of action of the hit xanthones <b>21</b> and <b>23</b> suggest that these two compounds affected similar molecular targets and cellular processes in mussel larvae, including that related to mussel adhesion capacity. This work exposes for the first time the relevance of C-1 aminated xanthones with a 3,4-dioxygenated pattern of substitution as new non-toxic products to prevent marine biofouling.

Giuseppe Paladini, Francesco Caridi, Vincenza Crupi et al.

A combination of Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) and 2D correlation analysis (2D-COS) was applied here for the first time in order to investigate the temperature-dependent dynamical evolution occurring in a particular type of inclusion complex, based on sulfobutylether-β-cyclodextrin (SBE-β-CD) as hosting agent and Coumestrol (7,12-dihydorxcoumestane, Coum), a poorly-soluble active compound known for its anti-viral and anti-oxidant activity. For this purpose, synchronous and asynchronous 2D spectra were calculated in three different wavenumber regions (960–1320 cm⁻¹, 1580–1760 cm⁻¹ and 2780–3750 cm⁻¹) and over a temperature range between 250 K and 340 K. The resolution enhancement provided by the 2D-COS offers the possibility to extract the sequential order of events tracked by specific functional groups of the system, and allows, at the same time, the overcoming of some of the limits associated with conventional 1D FTIR-ATR analysis. Acquired information could be used, in principle, for the definition of an optimized procedure capable to provide high-performance <i>T</i>-sensitive drug carrier systems for different applications.

Rachael Mooney, Wafa Abidi, Jennifer Batalla-Covello et al.

Abstract Background Immortalized, clonal HB1.F3.CD 21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored. Methods To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies. Results Here, we report efficient tumor tropism of HB1.F3.CD 21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting. Conclusions Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.

Tian-Tian Wang, Jing-Yi Liu, Rui Guo et al.

Metal-organic frameworks (MOFs) have been rapidly developed for their broad applications in many different chemistry and materials fields. In this work, a multi-dentate building block 5-(4-(tetrazol-5-yl)phenyl)-isophthalic acid (H₃L) containing tetrazole and carbolxylate moieties was employed for the synthesis of a two-dimensional (2D) lanthanide MOF [La(HL)(DMF)₂(NO₃)] (DMF = <i>N</i>,<i>N</i>-dimethylformamide) (<b>1</b>) under solvothermal condition. The fluorescent sensing application of <b>1</b> was investigated. <b>1</b> exhibits high sensitivity recognition for antibiotic nitrofurantoin (K_sv: 3.0 × 10³ M⁻¹ and detection limit: 17.0 μM) and amino acid <span style="font-variant: small-caps;">l</span>-tyrosine (K_sv: 1.4 × 10⁴ M⁻¹ and detection limit: 3.6 μM). This work provides a feasible detection platform of 2D MOFs for highly sensitive discrimination of antibiotics and amino acids.

Alain G. Giuglio-Tonolo, Christophe Curti, Thierry Terme et al.

Anthracycline antibiotics play an important role in cancer chemotherapy. The need to improve their therapeutic index has stimulated an ongoing search for anthracycline analogs with enhanced properties. This review aims to summarize the common synthetic approaches to benzo[<i>g</i>]quinoxaline-5,10-diones and their uses in heterocyclic chemistry. Because of the valuable biological activities of the 1,4-diazaanthraquinone compounds, a summary of the most promising heterocyclic quinones is provided together with their antitumor properties.

Jan Błaszczyk, Krzysztof Gasparski

The research was carried out on apples of the cultivar ‘Red Jonaprince’ in two storage seasons of 2015/2016 and 2016/2017. Both 1-MCP-treated and untreated apples were stored for 120 and 150 days at 2°C and 90–92% relative humidity in a regular cold store (NA) and in two atmospheric controlled storages, i.e. 2% CO2 and 2% O2 (CA) and 2% CO2 and 1.2% O2 (ULO). Apples were evaluated directly after the storage and after 7 days of simulated shelf-life. It was shown that storage conditions had significant impact on the value of apple quality traits. The effectiveness of the post-harvest 1-MCP treatment of apples manifested in different manner depending on the tested trait and storage conditions. 1-MCP delayed the softening of apples, but only those stored in CA and ULO. It effectively limited the decrease in titratable acidity, especially of apples from NA and ULO. A positive effect of 1-MCP in NA conditions on the soluble solids content was observed, as well as a reduction in the natural loss of weight and the percentage of fruits with the symptoms of fungal decay.

Dong-Sung Shin, Sung-Hoon Jung, Eun-Young Hong et al.

PURPOSE This study aimed to investigate whether hydrogen (H2) water drinking reduced oxidative damage products (8-hydroxy-2-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], L-lactate) produced in blood after exercise-induced oxidative stress. METHODS Men (n=7) and women (n=8) (systolic blood pressure [BP]: 90-150 mmHg, diastolic BP: 60-100 mmHg) were recruited. Exercise was performed for 20 minutes (8 km/hr) using treadmill. Placebo or test group drunk water and hydrogen water (1.2-1.5 ppm, 1,000 mL), respectively, right after exercise. Three days after, the same experiment was performed in the cross-over manner. Blood samples were obtained 30 minutes before exercise, right after exercise, and 30, 60, 120 minutes after exercise. 8-oxo-dG, MDA and L-lactate in serum were determined using ELISA kit. RESULTS The blood levels of 8-oxo-dG were significantly increased after exercise (from 381±9.4 to 524±14.9 ng/mL for male; from 367±13.5 to 509±10.7 ng/mL for female). In the placebo group, the increased 8-oxo-dG at each time was not significantly different from the peak level induced by the exercise except that at 120 minutes in female. In the test group, its levels at each time were significantly lower than that in the peak level. The effect of hydrogen water was more pronounced in female than in male. The results obtained with MDA were quite similar to those with 8-oxo-dG. The L-lactate levels were not significant statistically in both groups. CONCLUSIONS The data suggest that the one time drinking of hydrogen water may suppress the exercise-induced oxidative stress.

Ioanna Chinou, John Tsaknis, Vasilios Athanasiadis et al.

The antimicrobial activity of the oil extracted with n-hexane from the seeds of Moringa peregrina was tested against Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Candida albicans, C. tropicalis and C. glabrata. The oil proved effective against all of the tested microorganisms. Standard antibiotics (netilmycin, 5-flucytocine, intraconazole and 7-amino-4-methylcoumarin-3-acetic acid) were used for comparison. The resistance to oxidation of the extracted seed oil was also determined.

R Ramharack, M A Spahr, J S Kreick et al.

The apolipoprotein[a] (apo[a]) and plasminogen (PLG) genes share a high degree of sequence identity, suggesting that both genes may be coordinately expressed. To address this possibility, hepatic apo[a], PLG, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) mRNAs in 11 cynomolgus monkeys that express plasma Lp[a] over a 10-fold range (5.3-69.3 mg/dl) were measured. This analysis demonstrated a 13-fold variation in apo[a] mRNA. PLG mRNA levels ranged only 3-fold, which was similar to the deviation in G3PDH mRNA expression. Lp[a] and PLG plasma levels were also not related in the animals. To further define expression of the latter mRNAs, they were measured in liver and 13 extrahepatic tissues from 5 monkeys. Apo[a] transcript was detected for the first time in adrenal, lung, and pituitary in addition to brain and testes. PLG mRNA was detected extrahepatically only in testes while G3PDH mRNA was ubiquitously expressed. In individual animals, there was no relationship between hepatic and extrahepatic apo[a] mRNA levels suggesting tissue-dependent expression of the transcript. These results demonstrate that although the apo[a] and PLG genes are highly homologous, their mRNA expression differs markedly.

Jan ŠOBOTNÍK, František WEYDA, Robert HANUS et al.

The frontal gland as a sac-like organ in Prorhinotermes simplex is present only in presoldiers, soldiers, and imagoes, but exists also in nymph-soldier intercastes. The secretory epithelium consists of a single type of secretory cells adhering directly to the cuticular intima. Secretory vacuoles originate in electron dense vesicles, which are transformed into large electron lucent vacuoles. Intermediate vacuoles frequently contain lipid droplets. The frontal gland cells in presoldiers reveal modifications connected with the production of a new cuticle; the new cuticle is thin and compact, whereas the old one is thick, porous, and wrinkled. None of these cuticles is present in soldiers (sic!). In soldiers, the cuticular intima is of endocuticular origin and is formed by dispersed dense material; the apical parts of secretory cells are formed by numerous irregular finger-like projections, true microvilli are completely lacking. In imagoes, the cuticle is composed of an epicuticle, a layer of epicuticular filaments, and one more basal layer; sexual differences were not observed. In nymph-soldier intercastes, the structure of the gland differs in the head and in the metathorax; the head part of the gland resembles the imaginal gland whereas the thoracic part resembles more that of the soldier; the development of secretory vacuoles stops at the stage of presence of lipid droplets. E-1-nitropentadecene was found in the highest amount in soldiers (comparable to P. inopinatus soldiers), in moderate amount in imagoes, and it is missing in both presoldiers and intercastes.

JM Pepin, JA O'Neil, HF Hoff

Lipoprotein[a] or Lp[a] is a cholesterol-rich plasma lipoprotein that is associated with increased risk for cardiovascular disease. To better understand this association we determined the amount of apo[a] and apoB as possible estimates for Lp[a] and low density lipoprotein (LDL) accumulation in atherosclerotic lesions and in plasma, from patients undergoing vascular surgery, using specific radioimmunoassays for apolipoprotein[a] and apolipoprotein B. Apo[a] and apoB were operationally divided into a loosely bound fraction obtained by extracting minced samples of plaque with phosphate-buffered saline (PBS), and a tightly bound fraction obtained by extracting the residual tissue with 6 M guanidine-HCl (GuHCl). We found that 83% of all apo[a] but only 32% of all apoB in lesions was in the tightly bound fraction. When normalized for corresponding plasma levels, apo[a] accumulation in plaques was more than twice that of apoB. All fractions of tissue apo[a], loosely bound, tightly bound, and total, correlated significantly with plasma apo[a]. However, no significant correlations were found between any of the tissue fractions and plasma apoB. If all apo[a] and apoB had been associated with intact Lp[a] or LDL particles, the calculated mass of tightly bound Lp[a] would actually have exceeded that of tightly bound LDL in five cases with plasma Lp[a] levels above 5 mg apo[a] protein/dl. When PBS and GuHCl extracts of lesions were subjected to one-dimensional electrophoresis, the major band stained for lipid and immunoblotted positively for apo[a] and apoB, suggesting the presence of some intact Lp[a] in these extracts. These results suggest that Lp[a] accumulates preferentially to LDL in plaques, and that plaque apo[a] is directly associated with plasma apo[a] levels and is in a form that is less easily removable than most of the apoB. This preferential accumulation of apo[a] as a tightly bound fraction in lesions, could be responsible for the independent association of Lp[a] with cardiovascular disease in humans.