Activity Screening Research Articles

Phytochemistry and Biological Profile of the Chinese Endemic Herb Genus Notopterygium.

Notopterygium, a plant genus belonging to the Apiaceae family, is utilized in traditional Chinese medicine for its medicinal properties. Specifically, the roots and rhizomes of these plants are employed in phytotherapy to alleviate inflammatory conditions and headaches. This review provides a concise overview of the existing information regarding the botanical description, phytochemistry, pharmacology, and molecular mechanisms of the two Notopterygium species: Notopterygium incisum and N. franchetii. More than 500 distinct compounds have been derived from these plants, with the root being the primary source. These components include volatile oils, coumarins, enynes, sesquiterpenes, organic acids and esters, flavonoids, and various other compounds. Research suggests that Notopterygium incisum and N. franchetii exhibit a diverse array of pharmacological effects, encompassing antipyretic, analgesic, anti-inflammatory, antiarrhythmic, anticoagulant, antibacterial, antioxidant, and anticancer properties on various organs such as the brain, heart, digestive system, and respiratory system. Building activity screening models based on the pharmacological effects of Notopterygium species, as well as discovering and studying the pharmacological mechanisms of novel active ingredients, will constitute the primary development focus of Notopterygium medicinal research in the future.

Stabilization of TGF-β Receptor 1 by a Receptor-Associated Adaptor Dictates Feedback Activation of the TGF-β Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance.

Dysregulation of the transforming growth factor-β (TGF-β)signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug-resistant CSCs. Through a genome-wide CRISPR activation screen utilizing stem-like drug-resistant properties as a readout, the TGF-β receptor-associated binding protein 1 (TGFBRAP1) is identified as a TGF-β-inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF-β receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF-β signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly-ubiquitination and proteasomal degradation. Moreover, hyperactive TGF-β signaling in turn up-regulates TGFBRAP1 expression in drug-resistant CSC-like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF-β signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF-β signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1-mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF-β signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

Specificity of serological screening tests and reference laboratory tests to diagnose gambiense human African trypanosomiasis: a prospective clinical performance study

BackgroundSerological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future “screen and treat” strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening tests.MethodsDuring active screening, venous blood samples from 1095 individuals from Côte d’Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar.ResultsOne gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1–99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5–88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7–84.2%); DCN HAT RDT 78.2% (95% CI: 75.7–80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9–80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7–100% (n = 399) and 93.0–100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity.ConclusionsAlthough a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based “screen and treat” strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT.Trial registrationThe trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022.Graphical

In Vitro Antibacterial Activity of Three Traditionally Used Medicinal Plants against Multidrug Resistant Pseudomonas Aeruginosa

The current study involves the in-vitro screening of the antibacterial activities of three traditionally used therapeutic plants viz. Hippophae salicifolia, Phyllanthus emblica and Swertia chirayata against multidrug resistant Pseudomonas aeruginosa

Surface segregation phenomena encountered during solid carbon active screen plasma nitrocarburizing of AISI 316L

Plasma nitrocarburizing of an austenitic stainless steel AISI 316L was performed in an N2-H2 atmosphere (50 % H2 and 50 % N2) with a carbon-fiber reinforced carbon (CFC) active screen. The experimental concept of a plasma-discharged CFC active screen in conjunction with a substrate holder at floating potential ensures that no charged particles are present on the sample surface and no sputtering occurs. As a result, carbon contaminations are formed on the surface which were studied in detail with a combination of scanning electron microscopy (SEM) and secondary ion mass spectrometry (SIMS). The results indicate that a layer of about 25–50 nm of carbon is formed. At the same time, a strong segregation of Mn, Ni and Cr is observed below the coating within the steel substrate. Both effects progress with treatment time and there exists a clear correlation between the formation of the carbon layer and the segregation effect.

Screening, genotyping and haematological analysis of glucose-6-phosphate dehydrogenase deficiency in the blood donors of Wuxi City, China.

To investigate the prevalence, genotype and haematological characteristics of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the blood donor population of Wuxi area (Jiangsu Province, China) and to assess the impact of their red blood cell (RBC) units on clinical transfusion. We conducted genotyping and large-scale screening for G6PD enzyme activity in the blood donors of Wuxi City. In addition, we assessed the haematological parameters of G6PD-deficient and non-deficient blood donors, and investigated the adverse transfusion reactions in patients transfused with G6PD-deficient blood. We investigated 17,113 blood donors, among whom 44 (0.26%) were tested positive for G6PD deficiency. We identified 40 G6PD gene variants, among which c.1388G>A, c.1376G>T, c.1024C>T and c.95A>G were common. In addition, we identified two novel G6PD gene variants, c.1312G>A and c.1316G>A. The G6PD-deficient and non-deficient blood samples showed a significant difference in the RBC, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), RBC distribution width, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) values. However, the two samples showed no significant difference in the haemolysis rate at the end of the storage period. Finally, transfusion with G6PD-deficient RBC units did not lead to any adverse transfusion reactions. The positive rate of G6PD deficiency in the blood donor population of Wuxi City is 0.26%, and the genetic variants identified in this population are consistent with the common genetic variants observed in the Chinese population. Blood centres can establish a database on G6PD-deficient blood donors and mark their RBC units to avoid their use for special clinical patients.

Stilbene-pyridazinone hybrids: design, synthesis and in vitro antiplatelet activity screening

A series of stilbene analogues, in which a phenyl ring was replaced by the pyridazin-3(2H)-one nucleus, was designed and synthesized to be explored as platelet aggregation inhibitors. The proposed stilbene-pyridazinone hybrids were successfully obtained from simple starting materials and by Wittig’s reaction. Most of the target compounds displayed improved in vitro activity in comparison with the standard drug, resveratrol, highlighting as the most potent the analogues 10d and 10e, with inhibition percentages of 94.15 % at 100 µM and 100 % at 50 µM, respectively.The pharmacokinetic and toxicity (ADME/T) properties of the novel hybrids were also estimated with the SwissADME and ProTox-II web servers.

A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.

Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation. Through this approach, we identified a candidate proteolysis-targeting chimera (PROTAC), 22-SLF, that induces the degradation of FK506-binding protein 12 when the transcription of FBXO22 gene is activated. Subsequent mechanistic investigations revealed that 22-SLF interacts with C227 and/or C228 in F-box protein 22 (FBXO22) to achieve target degradation. Lastly, we demonstrated the versatility of FBXO22-based PROTACs by effectively degrading additional endogenous proteins, including bromodomain-containing protein 4 and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein.

Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs.

Emerging immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy have revolutionized cancer treatment and have improved the survival of patients with multiple cancer types. Despite this success many patients are unresponsive to these treatments or relapse following treatment. CRISPR activation and knockout (KO) screens have been used to identify novel single gene targets that can enhance effector T cell function and promote immune cell targeting and eradication of tumors. However, cancer cells often employ multiple genes to promote an immunosuppressive pathway and thus modulating individual genes often has a limited effect. Paralogs are genes that originate from common ancestors and retain similar functions. They often have complex effects on a particular phenotype depending on factors like gene family similarity, each individual gene's expression and the physiological or pathological context. Some paralogs exhibit synthetic lethal interactions in cancer cell survival; however, a thorough investigation of paralog pairs that could enhance the efficacy of cancer immunotherapy is lacking. Here we introduce a sensitive computational approach that uses sgRNA sets enrichment analysis to identify cancer-intrinsic paralog pairs which have the potential to synergistically enhance T cell-mediated tumor destruction. We have further developed an ensemble learning model that uses an XGBoost classifier and incorporates features such as gene characteristics, sequence and structural similarities, protein-protein interaction (PPI) networks, and gene coevolution data to predict paralog pairs that are likely to enhance immunotherapy efficacy. We experimentally validated the functional significance of these predicted paralog pairs using double knockout (DKO) of identified paralog gene pairs as compared to single gene knockouts (SKOs). These data and analyses collectively provide a sensitive approach to identify previously undetected paralog pairs that can enhance cancer immunotherapy even when individual genes within the pair has a limited effect.

Role of Optical Coherence Tomography (OCT), Fundus Photography, and Amsler Grid in Detection of Macular Disorders Associated with High Myopia

Abstract Background High myopia refers to ametropia characterized by elongation of optic axis and retinal and choroidal degeneration in the fundus, and high myopic patients present with various degrees of structural and functional retinal changes and thinning of the retinal thickness. Active screening for high myopic patients with imaging techniques by OCT, Fundus photography and amsler grid and providing patients with corresponding treatment on this basis may effectively reduce the risk of irreversible visual function damage. Objective To point to the importance of combining OCT, fundus photography with amsler grid testing in patients with high myopia. Methods This study was conducted on 40 eyes from EI-Demerdash Hospital outpatient clinic and ophthalmology department investigations unit in the period from June 2021 till May 2022; the patients were 24 females (60.0%) and 16 males (40.0%) with age ranged from 16 to 50 years. Results Our investigations gave us an idea about the macular diseases associated with high myopia and the importance of combining use of OCT, fundus imaging and amsler grid with patients with high myopia. These findings consist of chorioretinal atrophy, foveoschisis, choroidal neovascularization, dehiscence of retinal layers known as retinoschisis (foveoschisis or extre foveoschisis), macular holes (lamellar and full thickness), posterior retinal detachment. We can early detect theses changes in macula of highly myopic patients by Amsler grid testing as daily self monitoring and this can be useful in directing the patient to more sophisticated investigation tool like OCT and fundus photography and therefore give the patient the optimal chance to save the vision. Conclusion OCT combined with fundus photography and amsler grid testing are helpful tools that allow detailed evaluation of the macula in eyes with pathological myopia and easily anticipate, diagnose and follow up diseases associated with high myopia.

Edukasi Dan Deteksi Dini Hipertrigliseridemia Dalam Rangka Pencegahan Dan Pengelolaan Gangguan kognitif Pada Kelompok Lanjut Usia

Cognitive impairment is a neuropsychological condition characterized by a decline in cognitive functions that interferes with daily activities. Cognitive impairment in elderly can lead to the decrease in quality of life. One of the factors causing cognitive impairment is high triglyceride level. Therefore, this community service activity is carried out to increase awareness and knowledge about hypertriglyceridemia and cognitive disorders through education and health screening. The activity method with PDCA is implemented to ensure a systematic and effective approach. Preventive efforts are needed through education on healthy eating pattern, physical activity, and routine screening to control triglyceride levels and prevent cognitive impairment in the elderly.

Risk factors and molecular epidemiology of intestinal colonization by carbapenem-resistant Gram-negative bacteria in patients with hematological diseases: a multicenter case‒control study.

Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates.

Diagnostic accuracy of active pulmonary tuberculosis screening during detention admission: a systematic review.

Individuals entering incarceration are at high risk for infectious diseases, other ill conditions, and risky behavior. Typically, the status of active pulmonary tuberculosis (PTB) is not known at the time of admission. Early detection and treatment are essential for effective TB control. So far, no study has compared the diagnostic accuracy of various TB screening tools in detention using a network meta-analysis (NMA). We aimed to investigate the diagnostic accuracy of active PTB screening tests upon detention admission. We searched PubMed, Global Index Medicus, the Cochrane Library electronic databases, and grey literature for publications reporting detention TB entry screening in March 2022 and January 2024. Inclusion was non-restrictive regarding time, language, location, reference standards, or screening tests. Eligible study designs comprised comparative, observational, and diagnostic studies. Publications had to report TB screening of individuals entering confinement and provide data for diagnostic accuracy calculations. The QUADAS-2 tool was designed to assess the quality of primary diagnostic accuracy studies. This systematic review was registered with PROSPERO (CRD42022307863) and conducted without external funding. We screened a total of 2,455 records. Despite extensive searching, no studies met our inclusion criteria. However, we identified evidence revealing key differences in screening algorithm application. In conclusion, more diagnostic accuracy data on TB screening algorithms for detention admission worldwide needs to be collected. We recommend that global TB initiatives set up multi-site studies to investigate the diagnostic accuracy of TB screening on admission in low- and high-prevalence criminal justice systems. Further network meta-analyses of these studies could inform policymakers and public health experts to establish or fine-tune TB control in detention settings.

Clinical, Biochemical, Serological, Virological and Sonological Profile of Newly Diagnosed Patients of Chronic Hepatitis B Virus Infection – 422 Cases

Introduction: This retrospective study was done to see biochemical, serological and sonological status of newly diagnosed hepatitis B virus infected patients. Material and methods: Consecutive newly detected patients of chronic hepatitis B were included. Their epidemiological, clinical, biochemical, serological and sonographic findings were recorded. Data were analysed using (SPSS version20). Mean and percentage were calculated for continuous and categorical data respectively. Chi-square test was done and P value > 0.05 was taken as significant. Result: Total 422 patients, age from 11 to 75 years (mean 33.4) were included. Of them 317 (75.1%) and 105 (24.9%) were male and female respectively. Of them 320 (75.8%) were from rural areas, 253 (60.0%) were poor. Among them 216(51.18%) were detected during medical checkup for foreign job. And 173 (40.88%) had history saloon shave. In this series 144 (34.12%) patients were below 25 years and 216(51.18%) patients were within 26 to 45 years age group . ALT of patients varied from 10 iu/dl to 715 iu /dl (mean 51.63±48.40). Around50.5 % (n=213) had ALT within normal range (up to 40 iu/dl). HBeAg was positive in 97 (23.4%) patients. Hepatitis DNA (PCR) was not detectable in 135(32%) patients while it was above 100,000 copies / dl in 107(24.4%) patients. In this study 175 (53.84%) of patients with HBeAg negative had normal ALT and 83(61.48%) of patients with undetectable HBV DNA had normal ALT. Sonological examination was normal in 221 (%). Chronic liver disease, Hepatocellular carcinoma, ascites, fatty liver disease were detected in 60, 06(1.4%), 14 & 75 cases respectively. In this series, significant difference was found in DNA level (P= 0.029), hypertension status (P=0.013), ALT levels (P=0.00) and HBeAg status (P=0.000)in between sexes. HBeAg also varied significantly with ALT levels (P=0.011). ALT level also varied significantly between sexes (p= 0.00). Conclusion: Newly detected asymptomatic or symptomatic patients of chronic hepatitis B virus infected patients may have significant biochemical and serological viral activity requiring antiviral treatment. So mass screening and early detection of disease activity may improve outcome.

Chemical composition analysis of Ganoderma lucidum based on UPLC-Orbitrap-HRMS and virtual screening of FXR activators for treatment of liver fibrosis

The chemical composition of Ganoderma lucidum ethanol extracts was systematically analyzed and identified by ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS). The fragmentation pattern of the representative chemical compounds was summarized, and the potential anti-liver fibrosis active compounds of G. lucidum acting on the farnesoid X receptor(FXR) target were studied to elucidate its pharmacodynamic substance basis. Preliminarily, 95 chemical constituents of G. lucidum ethanol extracts were identified, including 24 ganoderic acids, 9 ganoderenic acids, 13 lucidenic acids, 3 ganolucidic acids, 1 ganoderma lactone, 40 other triterpenoids, 4 fatty acids, and 1 other constituent. In addition, the fragmentation patterns of the representative compounds were also analyzed. The structural characteristics of ganoderic acids and ganoderenic acids were the C30 skeleton, containing free-COOH and-OH groups, which could easily lose H_2O and CO_2 to form fragment ions. The D-ring was mostly a five-membered ring, which was prone to breakage. Lucidenic acids were the lanosterolane-type of the C27 skeleton, and the side-chain structure became shorter and contained the same free-COOH and-OH compared with ganoderic acids, which had been reduced from 8 to 5 cartons and prone to lose H_2O and CO_2. Then, six reported FXR receptor agonists were selected to form a training set for establishing a pharmacophore model based on FXR ligands. The 95 identified chemical constituents of G. lucidum were matched with the pharmacophore, and the optimal pharmacophore model 02(sensitivity=0.750 00, specificity=0.555 56, ROC=0.750) was selected for the virtual screening of the G. lucidum compound library through the validation of the test set. Finally, 31 potential G. lucidum active constituents were screened and chosen to activate the FXRs. The ADMET results showed that ganoderic acid H and lucidenic acid J had less than 90% plasma protein binding rate and no hepatotoxicity, which could be used as FXR activators for developing clinical drugs for the treatment of liver fibrosis, either alone or in combination.

The Effect of Two Health Education Packages on Nutritional Knowledge, Practices, and Physical Activity Levels Among School-Going Adolescents in Rishikesh: A Cluster Randomized Trial.

Introduction Adolescence is a critical period known for presenting specific challenges in disease treatment and health promotion. Studies have highlighted that increased nutritional awareness is associated with healthier eating habits, while regular physical activity aids in controlling and preventing non-communicable diseases. Equipping adolescents with health education in schools prepares them to adopt and maintain healthy lifestyles throughout their lives. To assess and compare the efficacy of health education packages targeting nutrition knowledge, practices, and physical activity levels, a cluster-randomized trial was conducted among school-going adolescents. Methodology Two distinct health education packages were developed for the two intervention groups. In group 1, a health talk supported by a flip chart was delivered, followed by pamphlet distribution. In contrast, in group 2, only information pamphlets were distributed. The study was conducted in government schools in Rishikesh, with four schools selected. Two schools were randomly allocated to each intervention arm. In each school, a questionnaire was administered to assess the students' nutrition knowledge, practicesand physical activity levels. This was followed by the intervention, and the students were reassessed for the same parameters after two weeks. Result The pre-intervention and post-intervention comparisons within the same group- the mean scores for nutrition knowledge, food practice, sleep duration, and recreational screen time were comparable in the intervention group 1 (p>0.05). There was a decrease in the mean physical activity score and screen time for studies in intervention group 1, and these differences were statistically significant (p<0.05). The mean scores for nutrition knowledge, physical activity, sleep duration, and screen time for studies were comparable in the intervention group 2 (p>0.05). There was an increase in the mean food practice score and a decrease in recreational screen time in intervention group 2, and these differences were statistically significant (p<0.05). On comparing the groups with each other, it was found thatGroup 2 exhibited a significantly higher mean food practice score compared to group 1 post-intervention. While there was a statistically significant decrease in the mean physical activity score in intervention group 1, this group still had higher physical activity levels than group 2.Post-intervention, group 2 exhibited a higher screen time for studies compared to group 1. Both groups had comparable sleep durations at baseline and post-intervention, with intervention group 1's mean sleep duration falling within the recommended range set by the American Academy of Sleep Medicine. Regression analysis provided valuable insights into the relationship between baseline values of various variables and their post-intervention values, aiding in understanding the impact of the health education packages. Conclusion The findings emphasize the significance of incorporating nutrition and physical activity education into the curriculum of students.

Synthesis of phenyl esters 2-oxo-2H-1-benzopyran-3-carboxylic acids as promising antimicrobial agents

Corresponding chloroanhydrides were synthesized by the interaction of coumarin-3-carboxylic and 6-methoxycoumarin-3-carboxylic acids with an excess of thionyl chloride under heating. Due to the quantitative yields and the formation of volatile products within the reaction, chloroanhydrides were used without additional purification in acylation of substituted phenols for the synthesis of phenyl esters of 2-oxo-2H-1-benzopyran-3-carboxylic acids. The reaction was carried out by heating in anhydrous dioxane environment in the presence of pyridine as a catalyst. The structure of the obtained esters was proven using instrumental methods of analysis. The antimicrobial and antifungal activity of the synthesized compounds was studied in vitro by the method of two-fold serial dilutions in liquid and solid nutrient environments. Antimicrobial activity screening showed that the synthesized esters have a moderate activity against gram-negative microorganisms and C. albicans. It was found that the 4-methyl-2-chlorophenyl ester of coumarin-3-carboxylic acid had the greatest bacteriostatic activity against Ps. aeruginosa and Pr. vulgaris, 2-chlorophenyl ester of coumarin-3-carboxylic acid against Ps. aeruginosa and E. coli, coumarin-3-carboxylic acid 4-hydroxyphenyl ester against Pr. vulgaris, and coumarin-3-carboxylic acid 2-isopropyl-5-methylphenyl ester against E. coli at a concentration of 31.25 g/ml. 2-Chlorophenyl ester also showed a bactericidal effect against E. coli. The synthesized compounds also have an antifungal effect against the C. albicans. strain used in the experiment. Thus, 4-methyl-2-chlorophenyl ester, 4-fluorophenyl ester, 4-hydroxyphenyl ester, 2,3-dihydroxyphenyl ester, 2-isopropyl-5-methylphenyl ester of coumarin-3-carboxylic acid are active at a concentration of 31.25 g/ml.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

Phytochemical Screening and Evaluation of Anti Diabetic Activity Using Momordica charantia (Leaf &amp; Stem) Extracts in Alloxan Induced Rats

Purpose: Current procedure is to find out the effect of anti-diabetic using Momordica Charantia (leaf and stem) extracts on Alloxan induced experimental rats. Methods: The leaf and stem extracts of Momordica charantia were prepared by using cold maceration technique. The obtained filtrates are then subjected to a distillation process to obtain pure and concentrated products. The phytochemical studies were performed for both the extracts. Wet granulation method was done for preparation of tablets. The α-Amylase inhibition assay was done to both leaf and stem extracts as an in vitro method and Alloxan induced anti diabetic method was done as an in vivo process for the experimental animals. At last creatinine and urea levels were estimated. Results: The phytochemical results of both leaf and the stem extracts were shown positive for phenols, tannins, flavonoids, glycosides, steroids, oils, fats and for alkaloids. The weight of the granules were reduced and found to be F1- 15.32gm, for granules F2-14.37gm, for granules F3-14.39gm and for granules F4- it was 13.83gm. For α-amylase inhibition assay the standard acarbose 58.70% of inhibition for 100 μg/ml concentrations, the leaf extract showed 80.58% of inhibition for 100μg/ml concentration and the stem extract showed 86.45% of inhibition for 100μg/ml concentration. In fasted rats for the extract-1 (leaf) the highest blood glucose level was seen at 0 min as 82(mg/dl) and for the extract-2(stem) the highest blood glucose level was seen at 0 min as 84(mg/dl). And for the Oral glucose tolerance test the extract-1(leaf) the highest blood glucose level was seen at 120 min as 119(mg/dl) and for the extract-2(stem) the highest blood glucose level was seen at 120 min as 108(mg/dl). Conclusion: The study attests to the therapeutic effects of the chosen plant extracts, which have been demonstrated to help prevent and regulate blood glucose levels. Furthermore, in managing diabetes and its associated problems. Momordica charantia plant extracts from the leaves and stems have demonstrated anti-hyperglycemic properties. The results of this investigation indicated that there was a notable antidiabetic response to the treatment using plant extracts (leaf &lt; stem).

Phytochemical and Pharmacological Screening for Anti-Thyroid Activity of Moringa Oleifera (Drumstick)

Phytochemical and Pharmacological Screening for Anti-Thyroid Activity of Moringa Oleifera (Drumstick)