High Levels Of Inhibition Research Articles

Engineered vildagliptin-loaded polymeric nanoparticles via microfluidic and spray drying for enhanced antidiabetic activity

Abstract Background Vildagliptin (VLG), an antidiabetic agent, presents a potential solution to this widespread affliction. It exhibits notable attributes, such as a high solubility and a shorter elimination half-life. The current study uses a microreactor to fabricate sustained-release VLG-encapsulated cross-linked chitosan–dextran sulfate nanoparticles (VLG-CDNPs). The fabrication was systematically optimized using the design of experiment approach. Results The optimized VLG-CDNPs had an average particle size of 217.4 ± 12.3 nm and an encapsulation efficiency of 78.25 ± 3.0%. Scanning electron microscopy revealed that the nanoparticles had a smooth spherical shape. Spray drying was used for drying, and the reconstitution ability was close to ideal (~ 1.33). In vitro studies revealed sustained VLG release over 12 h, with ~ 58% in acidic and ~ 83% in basic conditions. Cell viability remained at 80% even at 100 μg/mL, and glucose uptake in L6 cells was significantly enhanced with VLG-CDNPs (78.34%) compared to pure VLG (60.91%). VLG-CDNPs also showed moderate inhibitory activity against α-amylase (41.57%) and α-glucosidase (63.48%) compared to pure VLG, which had higher inhibition levels. Conclusion The study’s outcome suggested that the optimized VLG-CDNPs may serve as an effective and promising nanoformulation for managing diabetes mellitus.

Evaluation of Carrageenan-induced Anti-inflammatory Activity of Ethanolic Leaf Extract of Psychotria bisulcata Wight &Arn. in Wistar Rats

Psychotria bisulcata Wight & Arn. (Rubiaceae) is a shrub widely used in traditional medicine for the treatment of rheumatoid arthritis, diabetes, infertility and impotence. The present research work is focused on in vitro and in vivo anti-inflammatory activity in ethanolic leaf extract of P. bisulcata. The ethanol extract was subjected to in vitro anti-inflammatory assays such as hypotonic solution-induced hemolysis, heat-induced hemolysis. The in vitro anti-inflammatory assays revealed that the ethanolic leaf extract of P. bisulcata showed a high level of inhibition in hypotonic solution-induced hemolysis in 250 µg/mL as 55.80±1.91and in heat-induced hemolysis as 62.23±4.23. The in vivo anti-inflammatory activity was assessed using the carrageenan-induced paw edema model, with diclofenac as the standard. When compared to the standard diclofenac, the ethanolic leaf extract of P. bisulcata showed considerable anti-inflammatory efficacy in a dose dependent manner, resulting in the reduction of paw edema volume. The rats treated with ethanolic leaf extract of 500 mg/kg showed better activity. The research discovers that P. bisulcata has substantial anti-inflammatory action, indicating that it has medicinal potential in the treatment of inflammatory ailments.

A temperature-sensitive and less immunogenic Sendai virus for efficient gene editing.

Gene editing has the potential to be a powerful tool for the treatment of human diseases including HIV, β-thalassemias, and sickle cell disease. Recent advances have begun to overcome one of the major limiting factors of this technology, namely delivery of the CRISPR-Cas9 gene editing machinery, by utilizing viral vectors. However, gene editing therapies have yet to be implemented due to inherent risks associated with the DNA viral vectors typically used for delivery. As an alternative strategy, we have developed an RNA-based Sendai virus CRISPR-Cas9 delivery vector that does not integrate into the genome, is temperature sensitive, and does not induce a significant host interferon response. This recombinant SeV successfully delivered CRISPR-Cas9 in primary human CD14+ monocytes ex vivo resulting in a high level of CCR5 editing and inhibition of HIV infection.

BACE Inhibitor Clinical Trials for Alzheimer's Disease.

The amyloid hypothesis posits that the amyloid-β aggregates in the brain initiate a cascade of events that eventually lead to neuron loss and Alzheimer's disease. Recent clinical trials of passive immunotherapy with anti-amyloid-β antibodies support this hypothesis, because clearing plaques led to better cognitive outcomes. Orally available small molecule BACE1 inhibitors are another approach to slowing the buildup of plaques and thereby cognitive worsening by preventing the cleavage of amyloid-β protein precursor (AβPP) into amyloid-β peptide, the major component of plaques. This approach is particularly attractive because of their ease of use, low cost, and advanced clinical stage. However, although effective in preventing amyloid-β production in late-stage clinical trials, BACE inhibitors have been associated with early, non-progressive, likely reversible, cognitive decline. The clinical trials tested high levels of BACE inhibition, greater than 50%, whereas genetics suggest that even a 30% inhibition may be sufficient to protect from Alzheimer's disease. Aside from AβPP, BACE1 cleaves many other substrates in the brain that may be contributing to the cognitive worsening. It is important to know what the cause of cognitive worsening is, and if a lower level of inhibition would sufficiently slow the progress of pathology while preventing these unwanted side effects. Should these side effects be mitigated, BACE inhibitors could rapidly move forward in clinical trials either as a primary prevention strategy in individuals that are at risk or biomarker positive, or as a maintenance therapy following amyloid clearance with an anti-amyloid antibody.

Detection of Shiga toxin-producing Escherichia coli in dairy cows: genetic characterization and inhibition of adherence by cattle anti-STEC antibodies to HEp-2 cell.

Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen associated with severe disease. Cattle are recognized as the primary animal reservoir of STEC. This study reports the occurrence and characterization of STEC from dairy cows and evaluates the inhibition of adherence by cattle anti-STEC antibodies to the HEp-2 cell. From 151 samples, 30% (n = 45) were positive for stx by PCR screening (25.21% of dairy cows and 46.8% of growing calves). From these positive samples, 17 STEC isolates were characterized. In dairy cows, 3 out of 17 samples carried stx2, 3 out of 17 possessed stx1, and 2 out of 17 carried stx1/stx2. In growing cows, 8 out of 17 samples carried stx1 and 1 out of 17 carried stx1/stx2. Other virulence factors such as ehxA, saa, iha, cah, and eae were detected. The strains were typed into 3 E. coli O groups (O26, O91, and O130). The analysis of the HEp-2 adherence assays indicated that all serum from both cattle categories presented high levels of inhibition of adherence. Considering the severity of the symptoms caused by STEC in humans, searching for factors influencing the colonization of STEC in cattle would help identify strategies to avoid transmission and STEC infection.

EFFICACY OF SHRIMP SHELL SYNTHESIZED CHITOSAN AGAINSTPOST-HARVEST SPOILAGE FUNGI OF Sesamum indicum

Contamination of Agricultural commodities by moulds poses significant challenges due to conducive climatic conditions. Mycotoxins produced by moulds like Aspergillus, Penicillium, and Fusarium present health risks and economic losses. Traditional control measures such as the use of fungicides have drawbacks, necessitating the exploration of eco-friendly alternatives. One such alternatives is the use of Chitosan, a biopolymer derived from chitin found in crustacean exoskeletons. This study evaluated the efficacy of chitosan synthesized from shrimp shells in inhibiting the growth of Aspergillus niger, a common food borne mould of oil seeds such as Sesame. Synthesized Chitosan was characterized using FTIR spectroscopy, UV-visible spectroscopy, and the degree of deacetylation was determined. FTIR analysis showed characteristic absorption peaks ranging from 3911.77 cm-1 to 794.70 cm-1, with higher wave numbers corresponding to stretching vibrations of the C-H, O-H, and N-H bonds functional groups. UV-visible spectroscopy displayed an absorbance peak at 232 nm with an absorbance value of 2.15. The degree of deacetylation of synthesized chitosan was determined to be 98.99%. In vitro experiments showed a concentration-dependent inhibition of A. niger growth by shrimp shell synthesized chitosan. The highest level of inhibition was seen at day 3 with 0.75mg/ml (50%) and 1.0mg/ml (52.1%), meaning the higher the concentration of shrimp shell synthesized chitosan the higher the inhibition. Results suggest chitosan as a potential anti-fungal agent for food preservation and agricultural protection against mould contamination and mitigate post harvest losses and ensure food safety.

Trifolium repens extracts as a green corrosion inhibitor for carbon steel in a 3.5% NaCl solution

BackgroundMaterial degradation is a major issue that has been the subject of intense research and investigation by the scientific community. It has harmful consequences that require serious and careful intervention. However, restrictions on the use of inhibitors containing toxic compounds pose a significant challenge to the implementation of effective corrosion treatments. This has necessitated a continuous search for new and innovative ways to protect against material damage. Plant-derived natural inhibitors offer several advantages, including potent inhibitory effects, lack of toxicity, biodegradability, and environmentally sustainable origins. The purpose of this research was to evaluate the corrosion resistance of API5LX60 carbon steel in a 3.5 % NaCl environment using Trifolium repens as an environmentally friendly inhibitor. MethodsThe inhibitor extract was analysed using Fourier Transform Infrared (FTIR) spectroscopy. However, gravimetry and electrochemical methods (potentiodynamic polarization and electrochemical impedance spectroscopy (EIS)) were used to investigate the corrosion behaviour. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to examine the surface morphology. Significant findingsAfter testing a range of concentrations in a 3.5 % NaCl medium, the highest level of inhibition (98 %) was obtained at 20 ppm, confirming the mixed action of the inhibitor with predominantly cathodic action. The inhibition mechanism involved physical adsorption on metal surfaces according to the Langmuir model, which enhances the corrosion-inhibiting ability; the extract forms a protective layer that successfully inhibits corrosion, as confirmed through electrochemical and surface analysis. These results demonstrate that the extract acts as a potent anticorrosive agent.

The performance of hydrophilic moieties in synthesized fluorinated cationic surfactants on corrosion inhibition of carbon steel pipelines

Compared with traditional hydrocarbon surfactants, fluorinated surfactants exhibit unique characteristics such as reduced surface tension, enhanced efficacy in reducing interfacial tension, dual hydrophobic and oleophobic nature, increased thermal stability, and superior chemical resistance. These characteristics make them a favorite material for many kinds of applications. This study aims to highlight the synthetic route for three novel cationic fluorinated surfactants (CFS) and applied them in the oilfield as corrosion inhibitors. Characterization of the prepared surfactants took place using different spectroscopic techniques. The influence of hydrophilic moieties on the micellar characteristics of ionic surfactants that have the same hydrophobic fluorinated chains are investigated in this research. Also, an evaluation of the influence of these groups on thermodynamic parameters was carried out.The metal corrosion inhibition efficiency of the CFS was studied in acidic medium by three different techniques, including potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and weight loss procedures, at three different temperature ranges (25, 40, and 60 °C).The achieved results displayed the inhibition efficiency of the metal corrosion that was elevated by increasing both the CFS's concentration and the applied temperature values. The highest level of inhibition, reaching 97.48 %, was achieved at a concentration of 700 parts per million (ppm) and a temperature of 60 °C. Furthermore, it was noticed that the charge transfer resistance value was raised; however, the constant phase element was decreased with increasing the CFS concentrations. The CFS regards an excellent and mixed-type corrosion inhibitor. The adsorption of CFS has agreed the Langmuir's adsorption isotherm and was related to chemisorption. SEM photos show a good CS surface in the presence of CFS versus the absence of them.

Antimicrobial and Antiplasmodial Activities of Endophytic Fungi Associated with Psidium guajava

Infections due to antimicrobial-resistant microorganisms have become widespread in recent years. Thus, searching for novel antimicrobial agents to combat such pathogens has become crucial. The current study aimed to evaluate the antimicrobial, antiplasmodial, and immunomodulatory activities of the extracts of endophytic fungi isolated from Psidium guajava. Isolation, identification, fermentation, and extraction of the secondary metabolites of the fungal endophytes were carried out following standard procedures. The extracts were subjected to High-Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis to detect their bioactive components. The Antimicrobial activity and Minimum Inhibitory Concentration of the fungal extracts were evaluated against pure cultures of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia using Agar well diffusion and Agar dilution method respectively. The acute toxicity study (LD50) was carried out using Lorke’s method. The extracts were tested in vivo in mice for antiplasmodial activity against Plasmodium berghei and in vitro against Plasmodium falciparum using Peter and Reyley's curative test method and WHO standardized micro-test system with modification respectively. The immunomodulatory activity of the extracts was evaluated by cyclophosphamide-induced myelosuppression (hematological parameters). Active extracts were further subjected to Delayed-Type Hypersensitivity Response (DTHR) and Haemagglutination Inhibition Assay using Sheep Red Blood Cells as antigens. The result showed Alternaria sp. (PGL1, PGL2, PGL3), from P. guajava. The HPLC-DAD analysis revealed the presence of bioactive compounds previously reported to have antimicrobial, antiplasmodial, and immunomodulatory properties. The fungal extracts exhibited varying degrees of antimicrobial activity. The LD50 of the fungi extracts was>5000 mg/kg in mice. The extracts at 100 and 200 mg/kg body weight in mice showed varying degrees of antiplasmodial activity. Growth of P. berghei was significantly (p<0.001) inhibited, curative effect ranges from 59.09 – 100%. Schizont maturation of P. falciparum isolates was inhibited and the highest level of inhibition was observed at 1 mg/ml (p<0.05). The fungal extracts reversed the effect of cyclophosphamide-induced reduction in total white blood cell counts and % neutrophil. This study showed that the tested plant harbors species of endophytic fungi that contain numerous secondary metabolites. The endophytic fungi showed prophylactic, immunostimulatory, and antiplasmodial activities, which can be exploited to develop antimicrobial, antiplasmodial, and immunomodulatory agents.

Hydrogen-rich solution alleviates acute radiation pneumonitis by regulating oxidative stress and macrophages polarization.

This study was aimed to investigate the effect of hydrogen-rich solution (HRS) on acute radiation pneumonitis (ARP) in rats. The ARP model was induced by X-ray irradiation. Histopathological changes were assessed using HE and Masson stains. Inflammatory cytokines were detected by ELISA. Immunohistochemistry and flow cytometry were performed to quantify macrophage (CD68) levels and the M2/M1 ratio. Western blot analysis, RT-qPCR, ELISA and flow cytometry were used to evaluate mitochondrial oxidative stress injury indicators. Immunofluorescence double staining was performed to colocalize CD68/LC3B and p-AMPK-α/CD68. The relative expression of proteins associated with autophagy activation and the adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were detected by western blotting. ARP decreased body weight, increased the lung coefficient, collagen deposition and macrophage infiltration and promoted M1 polarization in rats. After HRS treatment, pathological damage was alleviated, and M1 polarization was inhibited. Furthermore, HRS treatment reversed the ARP-induced high levels of mitochondrial oxidative stress injury and autophagy inhibition. Importantly, the phosphorylation of AMPK-α was inhibited, the phosphorylation of mTOR and ULK1 was activated in ARP rats and this effect was reversed by HRS treatment. HRS inhibited M1 polarization and alleviated oxidative stress to activate autophagy in ARP rats by regulating the AMPK/mTOR/ULK1 signaling pathway.

Formulation and effectiveness of solid soap preparations from citronella grass (Cymbopogon nardus L.) essential oil extract against Listeria monocytogenes

Background: The components of essential oils, such as citronellol, citronellal, and geraniol have been reported to possess the ability to inhibit bacteria. Furthermore, Listeria monocytogenes is a bacteria that often affects humans and its infections can cause meningitis and bacteremia. In pregnant women, Listeria monocytogenes can cause flu-like syndrome with complications of miscarriage, infant death, and meningitis in infants. Objective: This study evaluated the suitability of solid soap preparations from Citronella grass essential oil, based on its physical properties, such as organoleptic tests, as well as assessments of chemical tests and the effectiveness of the sample produced against bacteria. Method: The soap-making process was initiated by mixing the fat fraction (stearic acid and coconut oil) with an alkali, namely 30% NaOH. The soap stock was then added to the other ingredients and stirred until it became homogeneous for testing. Results: The test showed a pH value, water content, total fat, ethanol insoluble material, free fatty acids, chloride content, and unsaponificable fat of 10.8, 14.26, 74.84, 2.4, 0.26, 0.48, and 85.8, respectively. Furthermore, the sample showed a high level of inhibition against Listeria monocytogenes. Conclusion: Evaluation of citronella essential oil extract soap met the requirements, except for its unsaponifiable fat.

Design, synthesis, and biological evaluation of aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7

Serotonin reuptake inhibition combined with the action targeting 5-hydroxytryptamine receptor subtypes can serve as a potential target for the development of antidepressant drugs. Herein a series of new aralkyl piperazines and piperidines were designed and synthesized by the structural modifications of the previously discovered aralkyl piperidine compound 1, targeting SSRI/5-HT1A/5-HT7. The results exhibited that compound 5a showed strong binding to 5-HT1A and 5-HT7 (Ki of 0.46 nM, 2.7 nM, respectively) and a high level of serotonin reuptake inhibition (IC50 of 1.9 nM), all of which were significantly elevated compared to 1. In particular, compound 5a showed weaker inhibitory activity against hERG than 1, and demonstrated good stability in liver microsomes in vitro. The preliminary screening using FST indicated that orally administered 5a, at a high dose, could reduce immobility time in mice markedly, indicating potential antidepressant activity.

Analysis of black rice and some other cereal grains for protein, sugar, polyphenols, antioxidant and anti-inflammatory properties

Cereal grains are the most consumed source of food for mankind. This study analyzed the nutritional status, polyphenol content, antioxidant, and anti-inflammatory activity of black rice and other commonly consumed cereal grains such as brown rice, white rice, barley, and wheat. For this, dried seed samples were grounded and extracted with 70 % ethanol. Among the grains, black rice was found rich in nutritional components like protein (15.81 ± 1.03%), free amino acid (2.69 ± 0.21%), and total sugar (4.61 ± 0.05%) content. However, barley was found rich in reduced sugar content (2.65 ± 0.03%). A functional component like polyphenol content (226.70 mg/g extract) was found to be the maximum in black rice. Black rice also showed high antioxidant activity where a small amount of black rice extract scavenged both 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (IC50, 99.73 μg/mL) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) (IC50, 204.60 μg/mL) free radicals. Anti-inflammatory activity analysis by inhibiting nitric oxide (NO) production revealed that black rice extracts had a higher level of inhibition (15.56 ± 1.05%) against NO production. So, nutritionally rich, and functionally potent black rice might be added or incorporated with our food items as a functional ingredient to uplift the nutritional status, antioxidant, and anti-inflammatory properties of food.

Peer Stress Spills Over to Family Stress in the Context of Emotion Regulation Difficulties: A Daily Diary Study with Chinese Adolescents

Conflict in peer and family relationships becomes more common in the adolescent period when compared to previous developmental periods. These typical developmental challenges can be exacerbated in the context of poor emotion regulation skills. Using daily diary data, the current study examined the stress spillover effects of peer and family stress on one another, as well as the moderating role of emotion regulation challenges (i.e., emotional inhibition, dysregulation). A sample of 310 Chinese adolescents (Mage = 13.02 years, SD = 0.76 years, 50.7% boys) completed an initial measure of emotion regulation difficulties, then reported on peer and family stress for 10 consecutive weekdays. Results indicated that there was an overall same-day peer stress spillover effect in which adolescents’ peer stress on a given day was negatively associated with later conflictual interactions with their parents. Further, the relation between peer stress and same- and next-day family stress was exacerbated in the context of high levels of emotional inhibition. Family stress did not significantly relate to next-day peer stress, nor was this association moderated by difficulties with emotion regulation. These results highlight the temporal sequence of daily peer-to-family stress spillover. Though emotional inhibition may be culturally adaptive for maintaining interpersonal harmony, it can be maladaptive in managing stress for Chinese adolescents.

Shrimp shell waste-modified natural wood and its use as a reservoir of corrosion inhibitor (L-arginine) for brass in 3% NaCl medium: Experimental and theoretical studies

The primary objective of this study is to harness the valuable properties of natural wood waste (NWW) and a shrimp shell extract known as chitosan (Cs). In this context, and in order to prevent rapid consumption of the L-arginine inhibitor (Arg), it was encapsulated in NWW by means of a chitosan polymer. The resulting modification was verified using X-ray diffraction (XRD), which revealed the presence of chitosan and reflections corresponding to arginine in the modified wood. Additional techniques, including Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM) coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), were used for comprehensive characterization. The corrosion inhibition effect resulting from the application of NWW-Cs-Arg composite was investigated using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The obtained results revealed that, at an optimal concentration of 2 g/L and under ambient temperature conditions (298 K), this composite demonstrated a high level of corrosion inhibition, reaching up to 75 %, exhibiting cathodic behavior. Quantum chemical calculations were also carried out to predict the active sites in the used inhibitor. The methodology employed was based on the B3LYP/6-311G++(d,p) theory in an aqueous environment. Parameters such as frontier molecular orbitals (HOMO and LUMO), global reactivity descriptors, molecular electrostatic potential (MEP), and Mulliken population have been studied to assess local reactivity and identify reactive centers and potential nucleophilic and electrophilic attack sites. Weak interactions were analyzed using topological approaches (ELF, LOL, and NCI). It is noteworthy that the arginine molecule interacts through hydrogen bonds between its guanidine group and the hydroxyl groups present in the wood and chitosan residues. Meanwhile, the amine groups of chitosan promote charge transfer between arginine and copper atoms, particularly through the NH groups in the alpha position relative to the C = O group.

Riceberry bran as a potential source of anti-diabetic agents and its Riceberry bran powder

This study evaluated the anti-a-glucosidase effect, antioxidant activity, and total phenolic compounds of Riceberry bran extracts prepared by the extraction of Riceberry bran with distilled water, ethanol, or hexane using a maceration technique. The ethanolic extract resulted in the significantly highest a-glucosidase inhibitory activity, at 64.13±1.09%. The highest levels of antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals were found in the aqueous extract with a half-maximal inhibitory concentration (IC50) of 0.26±0.001 and 0.13±0.001 mg/mL, respectively. Likewise, the total phenolic compounds of the aqueous extract were the highest at 36.20±1.80 mg GAE/g of extract. The Riceberry bran powder obtained by double drum drying was also examined for its physical and chemical properties. It was found that the Riceberry bran powder was of good quality and provided high levels of a-glucosidase inhibition (20.24±0.47%), antioxidant activities (IC50 for DPPH = 4.19±0.08 mg/mL, IC50 for ABTS = 1.57±0.07 mg/mL), and total phenolic compounds (31.25±1.32 mg GAE/g of powder). The overall results indicated the potential of Riceberry bran to provide a-glucosidase inhibitors, antioxidants, and phenolic compounds, which can be used as useful health promoters and nutraceuticals to combat diabetes, and its powder also had potential in the functional food industry.

FARKLI KURUTMA TEKNİKLERİNİN HURMA ERİĞİ MEYVELERİNİN (DIOSPYROS LOTUS L.) BİYOAKTİF, RENK, ANTİBAKTERİYEL VE DUYUSAL ÖZELLİKLERİ ÜZERİNE ETKİSİ

In this study, the effects of hot air drying (HD), vacuum drying (VD) and freeze drying (FD) processes on total phenolic (TPC) and flavonoid contents (TFC), antioxidant capacity (AC), color and antibacterial properties and sensory evaluation of date plum (DP) fruit were determined. Total phenolic, total flavonoid and antioxidant capacity values of dried and fresh samples were determined as 13.86-7.45 mg GAE/g, 7.17-4.09 mg CE/g and 86.60-54.98%, respectively. The highest inhibition levels against Bacillus cereus (24.50 mm) and Salmonella Typhimurium (24.67 mm), Yersinia enterocolitica (25.75 mm) and Staphylococcus aureus (25.17 mm) were determined for HD and VD, respectively. In terms of sensory evaluation, FD drying was scored similarly to fresh samples (P>0.05). Overall, FD drying could be applied for longer preservation of DP fruits in terms of bioactive properties, color and sensory evaluation.

New Dipterocarpol-Based Molecules with α-Glucosidase Inhibitory and Hypoglycemic Activity.

Dammarane triterpenoids are affordable and bioactive natural metabolites with great structural potential, which makes them attractive sources for drug development. The aim of the study was to investigate the potency of new dipterocarpol derivatives for the treatment of diabetes. Two dammaranes (dipterocarpol and its 20(24)-diene derivative) were modified by a Claisen-Schmidt aldol condensation to afford C2(E)-arylidenes in good yields. The majority of the synthesized compounds exhibited an excellent-to-moderate inhibitory effect toward α-glucosidase (from S. saccharomyces), among them eight compounds showed IC50 values less than 10 μM. 3-Oxo-dammarane-2(E)-benzylidenes (holding p-hydroxy- 3 l and p-carbonyl- 3 m substituents) demonstrated the most potent α-glucosidase inhibition with IC50 0.753 and 0.204 μM, being 232- and 857-times more active than acarbose (IC50 174.90 μM), and a high level of NO inhibition in Raw 264.7 cells with IC50 of 1.75 and 4.57 μM, respectively. An in vivo testing of compound 3 m (in a dose of 20 mg/kg) on a model of streptozotocin-induced T1DM in rats showed a pronounced hypoglycemic activity, the ability to reduce effectively the processes of lipid peroxidation in liver tissue and decrease the excretion of glucose and pyruvic acid in the urine. Compound 3 m reduced the death of diabetic rats and preserved their motor activity.

How Does Visual Temporal Processing Affect Chinese Character Reading in Children With Dyslexia? From the Perspective of Inhibition

Given that inhibition interacts with visual temporal processing (VTP), the past evidence regarding the influence of VTP on the Chinese character reading of children with dyslexia may not disclose the whole picture without considering inhibition. Thus, the present study is among the first to investigate VTP and cognitive inhibition as well as their relationships to Chinese character reading. We compared the performances of 62 Chinese-speaking children with dyslexia in primary school (n = 62, Mage = 11.36 years) on VTP and inhibition tasks to those in a chronological-age-matched group (CA; n = 62, Mage = 11.57 years) and reading-level-matched group (RL; n = 62, Mage = 8.98 years). The results revealed that children with dyslexia performed worse than both the CA-matched and RL-matched groups in VTP and inhibition after controlling for age, nonverbal intelligence, and attention. Moreover, the relationship between VTP and Chinese character reading was moderated by inhibition in children with dyslexia. VTP is positively related to Chinese character reading, but this relationship is observed only at higher levels of inhibition. Our results suggest that inhibition plays a potential role in VTP and Chinese character reading, especially for those with dyslexia whose proficiency in inhibition is not as intact as that of typically developing children.

Abstract 13963: Redefining the Assessment of “Therapeutic” Platelet Response to Acetylsalicylic Acid

Background: Despite extensive investigations, the optimal assessment of the “therapeutic response” to acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between serum thromboxane (Tx)B 2 ; arachidonic acid (AA)-induced platelet aggregation (PA) by light transmittance aggregometry (LTA); aspirin reaction units (ARU) by VerifyNow aspirin test (VN), and pharmacokinetics (PK). Methods: Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy volunteers. ASA response was defined as >95% inhibition of serum TxB 2, <550 ARU by VN test and ≤20% AA-induced PA. Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. Results: ASA Response measured by VN, and AA-induced PA was achieved within 30 minutes of ASA administration. A good correlation was observed between VN ARU and 1 mM AA-induced maximum PA (r=0.80, p<0.001), serum TxB 2 (r=0.76, p<0.001), and inhibition of serum TxB 2 (r=0.87, p<0.001). The relation between platelet aggregation and TxB 2 inhibition appears to be dichotomous, with only modest inhibition of TxB 2 (~50% inhibition) associated with marked inhibition of platelet aggregation. ROC curve analyses indicated that ≤558 ARU and ≤7% AA-induced PA were associated with >95% inhibition of TxB 2 . A plasma ASA 686 ng/mL cut-off was associated with >95% inhibition of serum TxB 2 , ≤7% 1 mM AA-induced PA by LTA, and ≤585 ARU. Conclusion: Our study demonstrated an important relationship between PD and PK parameters measured immediately following oral ASA and cutoff values for VN assay and LTA that is associated with >95% inhibition of serum TxB 2 . We demonstrated that ~50% inhibition of TxB 2 is required to reach high levels of platelet function inhibition.