Activity Screening Research Articles

Gardenin B, A Natural Inhibitor for USP7: In vitro Evaluation and In silico Identification

Background: Ubiquitin-specific protease 7 (USP7) is one of the most widely studied deubiquitin enzymes (DUBs). The protein level of USP7 is highly expressed in a variety of malignant cancers, which suggests that it is a prognostic marker of cancers and a potential drug target for oncotherapy. Objective: The aim of this study was to identify natural and effective USP7 inhibitors, in order to understand the activation of the USP7/p53 pathway by natural inhibitors. Methods: In this study, USP7 enzyme activity screening assay system and p53 luciferase reporter assay system have been applied for the discovery of natural USP7 inhibitors targeting the catalytic active site. Molecular docking and molecular dynamics (MD) simulation revealed the combined mechanism between USP7 with gardenin B. Results: The gardenin B was screened from our home-lab natural products (160 flavonoids) and had cytotoxicity in HCT116 cells (IC50 = 46.28 ± 2.16 μM). Preliminary in vitro studies disclosed its antiproliferative activity and activated p53 signaling pathway in HCT116 cells. We found that the complex formed by gardenin B and 5vsk (Ledock score = -6.86, MM/GBSA score = -53.35) had the optimal binding conformation. Moreover, the MD simulation showed that the π-π interactions between gardenin B with His461 and Phe409, and the hydrogen bonds interaction between gardenin B with Leu406 played an important role in maintaining the close binding of the complexes. Conclusion: In conclusion, gardenin B could be used as a natural product inhibitor of USP7 for further optimized design and development potential.

Activity Uji Aktivitas Antioksidan dan Kandungan Fitokimia Daun Benalu (Loranthus ferrugineus Roxb.) yang Tumbuh pada Ketinggian Tempat dan Inang Berbeda

Restrictions on synthetic antioxidants in several countries have caused the global community to switch to using natural antioxidants. One source of natural antioxidants is mistletoe leaves (Loranthus ferrugineus Roxb.).The presence of mistletoe in a place and host is an important aspect to pay attention to to get the best antioxidants. This research aims to determine the effect of different altitudes and host types on the antioxidant activity and phytochemical content of mistletoe leaves. This research was structured in a split-plot design with 2 factors, namely altitude (lowland and medium land) and host types (avocado, lime, cocoa, and dogfruit). Antioxidant activity test using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method and phytochemical screening using reagents. Variables observed included extract yield percentage, antioxidant activity (IC50 value), and phytochemical screening. The results showed that altitude and host type significantly affected the antioxidant activity of mistletoe leaves. Mistletoe leaves in avocado hosts in the lowlands and medium land showed the best antioxidant activity, namely 155,94 µg/mL and 156,25 µg/mL in the weak antioxidant category, and the highest phytochemical content, namely flavonoids, alkaloids, tannins, saponins, and steroids.

GC-MS-employed Phytochemical Characterization and Anticancer, Antidiabetic, and Antioxidant Activity Screening of Lagerstroemia Thorelli.

Lagerstroemia thorelli (L. thorelli) is a member of the Lythraceae family and has not been previously researched. Thus, this study aimed to investigate its unexplored potential and identify novel therapeutic prospects. This research evaluated antioxidant, antidiabetic, and cytotoxic potentials along with compound characterization of the ethanolic leaf extract of L. thorelli. The antioxidant potential was assessed using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical and hydrogen peroxide (H2O2) scavenging assays, total antioxidant capacity (TAC), total phenolic content (TPC), total flavonoid content (TFC) determination, antidiabetic property was assessed using α-amylase inhibition, and the cytotoxic effect was examined on HeLa and Vero cells using MTT colorimetric assay. Chemical characterization was performed using gas chromatography-mass spectrometry (GC-MS). The findings demonstrated strong antioxidant, strong antidiabetic, and moderate cytotoxic activities. Comprehensive phytochemical analysis revealed its abundance in flavonoids, phenols/phenolics, tannins, glycosides, steroids, resin, etc. GC-MS analysis of the L. thorelli extract identified 80 important compounds including cis-11-eicosenamide, beta-D-glucopyranoside, methyl-, alpha-D-glucopyranoside, methyl-, phthalic acid, gamma-sitosterol, phytol, silicic acid, squalene, butanoic acid, cyclobarbital, etc. which are well-documented for their antioxidant, antidiabetic, and anticancer effects. Thus, it can be inferred that L. thorelli could hold new promises in treating diseases like diabetes and free radical-induced conditions, including neurodegenerative diseases.

Design, synthesis, and biological evaluation of imidazolylacetophenone oxime derivatives as novel brain-penetrant agents for Alzheimer's disease treatment

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1−8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9−30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC50 value of 0.49 μM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aβ42 aggregation. Moreover, the selected nuclide [18F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment.

Exploring antiviral activity of Betanin and Glycine Betaine against dengue virus type-2 in transfected Hela cells

Dengue virus (DENV) infection is a worldwide public health concern infecting approximately 400 million individuals and about 40,000 mortalities yearly. Despite this, no licensed or readily available antiviral medication is currently available specifically for DENV infection, and therapy is typically symptomatic. Therefore, the objective of the study was to investigate the antiviral activity of Beta vulgaris L. phytoconstituents against DENV-2 targeting NS3 protein. The antiviral activity of phytochemicals was examined through virtual ligand-based screening, antiviral inhibition and dosage response assays, western blotting analysis and MD simulations. We conducted toxicological, and pharmacokinetic analysis to assess plant-based natural compound's efficacy, safety, and non-toxic doses. Molecular docking and MD simulation results revealed that the nonstructural protein-3 (NS3) might prove as a funamental target for Betanin and Glycine Betaine against Dengue virus. Betanin and Glycine betaine were initially studied for their non-toxic doses in HeLa, CHO, and Vero cells via MTT assay. HeLa cells were transiently transfected with cloned vector pcDNA3.1/Zeo(+)/DENV-2 NS3 along with non-toxic doses (80 μM–10 μM) of selected phytochemicals. The dose-response assay illustrated downregulated expression of DENV-2 NS3 gene after administration of Betanin (IC50 = 4.35 μM) and Glycine Betaine (IC50 = 4.49 μM). Dose response analysis of Betanin (80 μM–10 μM) depicted the significant inhibition of NS3 protein expression as well. These results suggested downregulated expression of DENV-2 NS3 at mRNA and protein level portraying the DENV replication inhibition. Based on our study findings, NS3 protease is depicted as distinctive DENV-2 inhibitor target. We will channel our study further into in vitro characterization employing the mechanistic study to understand the role of host factors in anti-flavi therapeutic.

Design, synthesis and activity screening of cedrol derivatives as small molecule JAK3 inhibitors

The JAK-STAT signalling pathway is considered to be a significant role involved in the regulation of inflammatory diseases and immune responses, which indicate that specific inhibition of JAK-STAT pathway would be a potential key strategy for RA (Rheumatoid arthritis) treatment. Cedrol (CE), found from ginger by our group earlier, has been proven to play an excellent role in ameliorating RA via acting on JAK3. In this study, 27 new (1, 3–28), along with one known (2) derivatives of CE were synthesized by using chloroacetic acid and acryloyl chloride as intermediate ligands. In vitro, the inhibition effect on JAK kinases were performed using HTRF (Homogenous Time-Resolved Fluorescence) detection technology, which is more convenient and stable than traditional methods. The results compared with the secretion of LPS-induced p-JAK3 can better reflect the true kinase-selective effect of the compounds. Compound 22 was identified as a potent inhibitor to reduce the secretion of LPS-induced p-JAK3 with a dose-dependent manner. Given these results, compound 22 could serve as a favourable inhibitor of JAK3 for further research.

Preliminary Screening of Phytochemicals and Antibacterial Activity of Medicinal Plant Ber (<i>Ziziphus mauritiana</i> Lamark)

The most important genus in the Rhamnaceae family is Ber (Ziziphus mauritiana Lamk). Phytochemicals present in Ziziphus have antioxidant as well as antimicrobial properties. The present study aimed to detect various phytochemicals and evaluate the antibacterial activity in the Z. mauritiana leaf extracts. Leaves from 14 cultivars/germplasm/varieties of Z. mauritiana were used to explore the presence of various phytoconstituents such as alkaloids, flavonoids, cardiac glycosides, phenols, saponins, protein, steroids, tannins, lignins, and reducing sugar. These phytoconstituents have antioxidant, antibacterial, and hepatoprotective activities. The preliminary antimicrobial activity screening of Ziziphus leaf extract against bacterial strains-Bacillus subtilis (Gram-positive), Staphylococcus aureus (Gram-positive), Salmonella abony (Gram-negative), E. coli DH5α (Gram-negative) were performed by using well diffusion method. The results of various phytochemicals like alkaloids, phenolics, flavonoids, tannins, carbohydrates, proteins, lipids, and amino acids were reported in all selected commercial varieties/cultivars/ germplasm. On the other hand, saponins were found completely absent in methanolic solvents of all varieties/cultivars. The aqueous and methanolic solvent leaf extract were tested for antibacterial activity at different concentrations (25mg/ml, 50mg/ml, and 100mg/ml) against the bacterial strains of B. subtilis, S. aureus, S. abony, and E. coli DH5α, respectively. This study showed that the phytochemicals extracted from Z. mauritiana leaves have potential antimicrobial activities.

Discovery and Biosynthesis of Persiathiacins: Unusual Polyglycosylated Thiopeptides Active Against Multidrug Resistant Tuberculosis.

Thiopeptides are ribosomally biosynthesized and post-translationally modified peptides (RiPPs) that potently inhibit the growth of Gram-positive bacteria by targeting multiple steps in protein biosynthesis. The poor pharmacological properties of thiopeptides, particularly their low aqueous solubility, has hindered their development into clinically useful antibiotics. Antimicrobial activity screens of a library of Actinomycetota extracts led to discovery of the novel polyglycosylated thiopeptides persiathiacins A and B from Actinokineospora sp. UTMC 2448. Persiathiacin A is active against methicillin-resistant Staphylococcus aureus and several Mycobacterium tuberculosis strains, including drug-resistant and multidrug-resistant clinical isolates, and does not significantly affect the growth of ovarian cancer cells at concentrations up to 400 μM. Polyglycosylated thiopeptides are extremely rare and nothing is known about their biosynthesis. Sequencing and analysis of the Actinokineospora sp. UTMC 2448 genome enabled identification of the putative persiathiacin biosynthetic gene cluster (BGC). A cytochrome P450 encoded by this gene cluster catalyzes the hydroxylation of nosiheptide in vitro and in vivo, consistent with the proposal that the cluster directs persiathiacin biosynthesis. Several genes in the cluster encode homologues of enzymes known to catalyze the assembly and attachment of deoxysugars during the biosynthesis of other classes of glycosylated natural products. One of these encodes a glycosyl transferase that was shown to catalyze attachment of a D-glucose residue to nosiheptide in vitro. The discovery of the persiathiacins and their BGC thus provides the basis for the development of biosynthetic engineering approaches to the creation of novel (poly)glycosylated thiopeptide derivatives with enhanced pharmacological properties.

Combatting Fungal Infections: Advances in Antifungal Polymeric Nanomaterials.

Fungal pathogens cause over 6.5 million life-threatening systemic infections annually, with mortality rates ranging from 20 to 95%, even with medical intervention. The World Health Organization has recently emphasized the urgent need for new antifungal drugs. However, the range of effective antifungal agents remains limited and resistance is increasing. This Review explores the current landscape of fungal infections and antifungal drugs, focusing on synthetic polymeric nanomaterials like nanoparticles that enhance the physicochemical properties of existing drugs. Additionally, we examine intrinsically antifungal polymers that mimic naturally occurring peptides. Advances in polymer characterization and synthesis now allow precise design and screening for antifungal activity, biocompatibility, and drug interactions. These antifungal polymers represent a promising new class of drugs for combating fungal infections.

Public Perceptions on the Use of the Physical Activity Readiness Questionnaire.

Self-administered pre-participation screening for physical activity (PA) requires an instrument that should be easily used and identify individuals at high risk. The Physical Activity Readiness Questionnaire (PAR-Q+) has been used for many years. Its ease of use and ability to identify those not fit to undergo PA has not been assessed. This study was to determine the rates of the PAR-Q+ in identifying adults who may not be fit for moderate or intense PA and obtain feedback on the use of this tool. A randomized, cross-sectional study involving a wide spectrum of members of the public was carried out. Participants were asked to provide their bio-characteristics, complete the PARQ+, and provide feedback on the questionnaire. With 1019 participants, about 33.1% of the participants using the PARQ+ would have required further medical evaluation. Except for those patients with respiratory illness, there was no difference in levels of PA in those who answered yes or no to the seven PARQ+ questions. Only 4 of the 7 main PAR-Q+ questions were perceived by the public as easily understood. Difficulties were encountered with 21 of the 45 follow-up questions, especially amongst those with co-morbidities. The wordiness of the questions and the large number of technical terms were also sources of concern. Suggestions were provided by participants on areas where improvements may be made to the wording of the questions. The study suggests that the PAR-Q+ probably over-identified those who require further medical evaluation. In addition, the wordiness of the questions and frequent use of medical jargon made the PARQ+ challenging to understand and use. The suggestions provide opportunities to review areas for possible improvements.

Genome-Wide Association Studies Reveal That the Abietane Diterpene Isopimaric Acid Promotes Rice Growth through Inhibition of Defense Pathways.

Plants are an important source for the discovery of novel natural growth regulators. We used activity screening to demonstrate that treatment of Nipponbare seeds with 25 μg/mL isopimaric acid significantly increased the resulting shoot length, root length, and shoot weight of rice seedlings by 11.37 ± 5.05%, 12.96 ± 7.63%, and 27.98 ± 10.88% and that it has a higher activity than Gibberellin A3 (GA3) at the same concentration. A total of 213 inbred lines of different rice lineages were screened, and we found that isopimaric acid had different growth promotional activities on rice seedlings of different varieties. After induction with 25 μg/mL isopimaric acid, 15.02% of the rice varieties tested showed increased growth, while 15.96% of the varieties showed decreased growth; the growth of the remaining 69.02% did not show any significant change from the control. In the rice varieties showing an increase in growth, the shoot length and shoot weight significantly increased, accounting for 21.88% and 31.25%. The root length and weight significantly increased, accounting for 6.25% and 3.13%. Using genome-wide association studies (GWASs), linkage disequilibrium block, and gene haplotype significance analysis, we identified single nucleotide polymorphism (SNP) signals that were significantly associated with the length and weight of shoots on chromosomes 2 and 8, respectively. After that, we obtained 17 candidate genes related to the length of shoots and 4 candidate genes related to the weight of shoots. Finally, from the gene annotation data and gene tissue-specific expression; two genes related to this isopimaric acid regulation phenotype were identified as OsASC1 (LOC_Os02g37080) on chromosome 2 and OsBUD13 (LOC_Os08g08080) on chromosome 8. Subcellular localization analysis indicated that OsASC1 was expressed in the plasma membrane and the nuclear membrane, while OsBUD13 was expressed in the nucleus. Further RT-qPCR analysis showed that the relative expression levels of the resistance gene OsASC1 and the antibody protein gene OsBUD13 decreased significantly following treatment with 25 μg/mL isopimaric acid. These results suggest that isopimaric acid may inhibit defense pathways in order to promote the growth of rice seedlings.

Individualized activity recommendation based on a physical fitness assessment increases short- and long-term regular physical activity in people with multiple sclerosis in a retrospective cohort study.

Despite the evidence of beneficial effects of physical activity (PA), people with multiple sclerosis (pwMS) are less physically active than the general population. To increase PA in pwMS, we developed a structured individually tailored PA promotion program which is conducted within clinical practice in a university-based outpatient clinic since 2016. This study serves as retrospective quality control of this program. In a retrospective cohort study, we assessed the physical fitness of pwMS and the impact of the program on short- and long-term PA changes and behavioral determinants. The program consisted of four appointments each 2-4 weeks apart. Spiroergometric test results of female pwMS were compared to female non-MS controls who underwent a voluntary physical fitness analysis. The short version of the Freiburger questionnaire, self-developed questions and the modified Physical activity screening questionnaire (PASQ) were sent to all participants assessing the PA levels before the program, 3 months after the program (short-term), and at the time of the survey (long-term). Additionally, established questionnaires assessed behavioral determinants before the program and long-term. A total of 166 participants [mean age 38.32 (± 10.61 SD), mean EDSS 2.30 (±1.29 SD)] and mostly females (63.3%, n = 105) were included in the study and started the program. A total of 136 participants completed the program. Out of these 63.9% (n = 87) answered the questionnaires in 12.38 (±11.34 SD) months after finishing the program. At baseline female pwMS (n = 100) showed a lower physical fitness in comparison to non-MS controls (n = 26) (maximal workload (Watts): 138.86 ± 37.85 vs. 191.73 ± 45.25, p < 0.001; peak oxygen consumption (ml min-1 kg-1): 26.40 ± 7.23 vs. 31.56 ± 10.10, p = 0.020). pwMS were more regularly active in short- (62.1%) and long-term (55.2%) compared to baseline (24.2%, p < 0.001). Among the activated participants, we observed improved internal motivation (p = 0.002) and decreased perception of barriers (p = 0.006) compared to baseline. PwMS showed a lower physical fitness in comparison to non-MS controls. An individually tailored PA promotion program might improve behavioral determinants and thereby increase short- and long-term PA levels of pwMS.

Post kala-azar dermal leishmaniasis burden at the village level in selected high visceral leishmaniasis endemic upazilas in Bangladesh

ObjectivesAs post kala-azar Dermal Leishmaniasis (PKDL) threatens the success of the Visceral Leishmaniasis (VL) elimination initiative, we aimed to investigate the PKDL burden, including an active search for PKDL in leprosy-negative skin lesion cases. We also investigated their health-seeking behavior and perceived level of stigma. MethodsThis was a cross-sectional survey among inhabitants in the VL-endemic villages of the five most VL-endemic upazilas. VL experts trained medical officers in Upazila Health Complexes (UHCs) and leprosy facilities in PKDL management. Frontline workers conducted house-to-house surveys, referring PKDL suspects to designated centers. Data analysis involved Epi Info version 7 and IBM SPSS Statistics 25. ResultsAmong 472,435 screened individuals, 4022 had past VL (0.85 %). Among the screened population, 82 were PKDL suspects, and 62 PKDL cases were confirmed. The overall PKDL burden was 1.3 (95 % CI: 1.0-1.7) in the 10,000 population in the endemic villages. Male predominance and macular form of PKDL were observed. Thirty-nine PKDL patients perceived stigma of different levels. Only 27 of 62 (44 %) had received PKDL treatment. Medicine's unavailability and side effects were a major reason behind treatment interruption. Active screening among 137 leprosy-negative PKDL suspects yielded 10 (7.3 %) PKDL cases. ConclusionThe existence of PKDL cases in the VL endemic areas is a concern as those are inter-epidemic reservoirs. As per the WHO roadmap, the PKDL burden must be reduced by 70 % and 100 %, respectively, by 2026 and 2030. NKEP can take the current burden of 1.3 per 10,000 people in VL endemic villages as a baseline. Integrating active case detection for PKDL in leprosy hospitals and screening centers is feasible and worth deploying nationwide.

Screening for antibacterial activity of Cissampelos pareira L. root extract: an in-vitro study

Screening for antibacterial activity of Cissampelos pareira L. root extract: an in-vitro study

Enabling Modular Click Chemistry Library through Sequential Ligations of Carboxylic Acids and Amines.

High-throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double-click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO2NCO) via a modular amidation/SuFEx (sulfur-fluoride exchange) process. This method provides facile access to chemical libraries of N-fluorosulfonyl amides (RCONHSO2F) and N-acylsulfamides (RCONHSO2NR'R'') in near-quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96-well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram-positive bacterium S. aureus and drug-resistant MRSA (MIC up to 6.25 μg ⋅ mL-1). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high-throughput medicinal chemistry.

Enabling Modular Click Chemistry Library through Sequential Ligations of Carboxylic Acids and Amines

AbstractHigh‐throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double‐click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO2NCO) via a modular amidation/SuFEx (sulfur‐fluoride exchange) process. This method provides facile access to chemical libraries of N‐fluorosulfonyl amides (RCONHSO2F) and N‐acylsulfamides (RCONHSO2NR′R′′) in near‐quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96‐well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram‐positive bacterium S. aureus and drug‐resistant MRSA (MIC up to 6.25 μg ⋅ mL−1). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high‐throughput medicinal chemistry.

Cytotoxic and Anti-HSV-1 Effects of Caulerpin Derivatives.

Marine organisms represent a potential source of secondary metabolites with various therapeutic properties. However, the pharmaceutical industry still needs to explore the algological resource. The species Caulerpa lamouroux Forssk presents confirmed biological activities associated with its major compound caulerpin, such as antinociceptive, spasmolytic, antiviral, antimicrobial, insecticidal, and cytotoxic. Considering that caulerpin is still limited, such as low solubility or chemical instability, it was subjected to a structural modifications test to establish which molecular regions could accept structural modification and to elucidate the cytotoxic bioactive structure in Vero cells (African green monkey kidney cells, Cercopithecus aethiops; ATCC, Manassas, VA, USA) and antiviral to Herpes simplex virus type 1. Substitution reactions in the N-indolic position with mono- and di-substituted alkyl, benzyl, allyl, propargyl, and ethyl acetate groups were performed, in addition to conversion to their acidic derivatives. The obtained analogs were submitted to cytotoxicity and antiviral activity screening against Herpes simplex virus type 1 by the tetrazolium microculture method. From the semi-synthesis, 14 analogs were obtained, and 12 are new. The cytotoxicity assay showed that caulerpin acid and N-ethyl-substituted acid presented cytotoxic concentrations referring to 50% of the maximum effect of 1035.0 µM and 1004.0 µM, respectively, values significantly higher than caulerpin. The antiviral screening of the analogs revealed that the N-substituted acids with methyl and ethyl groups inhibited Herpes simplex virus type 1-induced cytotoxicity by levels similar to the positive control acyclovir.

SCREEN TIME IN PRESCHOOL-AGED CHILDREN

The World Health Organization defines sedentary screen time as the time spent in passive screen-based entertainment (TV, computer, mobile phone), excluding active screen time, specifically time spent playing games requiring physical activity or movement. Researchers agree that preschool-aged children spend longer periods of time in front of screens than recommended for their age, contradicting WHO guidelines on sedentary screen time for children up to 5 years old. The aim of our research was to obtain data on the age at which children are first exposed to screens, determine the duration of screen exposure on a daily basis, the most common type of screen, and the situations in which preschool-aged children use them. The sample consisted of 200 children, aged 48 to 60 months, of both genders. A specially constructed sociodemographic questionnaire was used for the research, which included questions regarding the age at which the child was first exposed to screens, the duration of daily exposure, as well as the most common type of screen and situations in which the child uses them. Informants were the parents of the children included in the study. The research was conducted in preschool institutions in Bosnia and Herzegovina, during February and March 2024. The results of the research show that children are first exposed to screens as early as at the age of 7 to 12 months, and that screen exposure on a daily basis exceeds the recommended time by WHO guidelines for most participants. The most common type of screen to which children are exposed is TV, and the most common situations in which they use them are during meals or while parents perform various household chores. Attention should be directed towards further identifying factors leading to excessive screen usage and providing clear guidelines to parents regarding the timing, content, technology, and joint activities related to screen time for young children in various cultural settings.

The leaf essential oil of Ecuadorian Ophryosporus peruvianus (J.F. Gmel.) R.M. King & H. Rob: chemical composition, enantioselective analysis, and in vitro enzymatic inhibitory activity

ABSTRACT An Ecuadorian specimen of Ophryosporus peruvianus produced an essential oil with a yield of 0.4% of the weight of the fresh plant material. A total of thirty-two compounds were detected and quantified. The chemical composition showed the predominance of monoterpene hydrocarbons, with sabinene (22.5%), β-pinene (15.1%), limonene (8.3%), β-phellandrene (29.7%), δ-elemene (2.1%), and epi-α-cadinol (2.7%) being the main components, expressed as mean values on two stationary phases of different polarity. This composition was very different from that reported in the literature for the essential oil of a Peruvian specimen, which was dominated by sesquiterpene hydrocarbons. These results indicate the existence of different chemotypes of O. peruvianus. Moreover, an enantioselective analysis of the major chiral constituents was performed, which revealed (R)-(-)-β-phellandrene, (R)-(-)-β-phellandrene and (1R,9R,E)-(-)-β-caryophylleneas enantiomerically pure compounds. On the other hand, β-thujene, β-pinene, β-pinene, sabinene, limonene, and terpinen-4-ol were scalemic mixtures. Finally, a preliminary screening of enzymatic inhibitory activity was performedin vitro, showing modest but interesting inhibition of both butyrylcholinesterase and lipase.

Active vs Passive Screening for Colorectal Cancer: Insights From the National Colonoscopy Study.

Active vs Passive Screening for Colorectal Cancer: Insights From the National Colonoscopy Study.