Search

Abstract Background Trends in cannabis use suggest a global increase in the past decade. Current evidence associates cannabis use with an increased risk of psychosis. This association has prompted a growing research interest in the association between cannabis use and psychiatric disorders, especially psychotic disorders. This study aims to gain a better understanding of the effect of cannabis on psychosis and its clinical progression. Results We conducted a retrospective chart review of cannabis use in patients hospitalized for a psychosis episode over five years at the American University of Beirut Medical Center (AUBMC). Cannabis users were more likely to be young single males using other substances compared to non-cannabis users. Frequent cannabis use was associated with a higher likelihood of paranoia and legal problems. Other psychotic symptoms did not significantly differ between frequent cannabis users and non-users. The length of hospital stay and the duration of the psychotic episode did not significantly differ between cannabis users and non-users. Family stressors and family history of a psychotic disorder were associated with a higher likelihood of personal history of violence. Conclusions This study is the first in Lebanon to reproduce findings supporting the association between cannabis and psychosis previously highlighted in other populations. Further prospective research is needed to better understand the effect of cannabis use on psychosis and to accordingly revise policies on cannabis legalization to reduce the global burden of psychotic disorders.

The present study aimed to show how the vegetation structure in the southern part of the Gelibolu (Gallipoli) Peninsula (south of the Eceabat-Kabatepe Highway) is formed according to the site characteristics. For this purpose, 100 sample areas each with a size of 400 m2 were taken. Proportions of the trees, bushes and perennial plants in the sample areas were assessed according to the Braun-Blanquet method. In order to determine the general soil characteristics of the study area, topsoil samples were taken at 0–30 cm depth level from 51 sample areas and the bedrock type was determined. Analyses were made on the soil samples for soil reaction (pH), lime, organic carbon, total nitrogen and texture. Additionally, coordinate, elevation, aspect and slope determinations were made in each sample area. For assessments,in consideration of geographical characteristics and especially topographic structure, the study field was divided into 6 different districts, and the vegetation structure was examined at these 6 districts. As a result of study, 61 different plant species were determined, and it was found that especially topographic structure and aspect were very influential on the distribution of these species. The influence of aspect can be explained by the effects of insolation and prevailing wind on field moisture. The study also determined that individuals of the species in wind-exposed areas and especially in areas close to seashore were often shorter and deformed compared to those in areas sheltered from wind. This can be explained by the fact that where the Mediterranean climate is dominant, plants reduce their above-ground parts for avoiding exposure to physiological drought because strong winds trigger transpiration.

Background: Individuals infected with the COVID-19 virus present with different symptoms of varying severity. In addition, not all individuals are infected despite exposure. Risk factors such as age, sex, and comorbidities play a major role in this variability; however, genetics may also be important in driving the differences in the incidence and prognosis of the disease. An Insertion/Deletion (I/D) polymorphism in the ACE1 gene (rs1799752) may explain these genetic differences. The aims of this study were to determine the potential role of ACE1 I/D genetic polymorphism in the risk of contracting COVID-19 as well as predicting the severity of COVID-19 infection.Methods: Three-hundred and eighty-seven non-related Lebanese subjects, 155 controls and 232 cases, who presented to the American University of Beirut Medical Center (AUBMC) for COVID-19 PCR testing were recruited. Clinical data were collected via filling a questionnaire and accessing the medical records. Peripheral blood was withdrawn for DNA isolation, and genotyping performed with standard PCR followed by band visualization on agarose gel.Results: In our study population, previously described risk factors such as gender, age, and comorbidities were associated with increase in disease susceptibility and severity. ACE1 I was the least common allele, and there was a positive association between ACE1 I and the risk of contracting the COVID-19 disease. More specifically, the frequency of II genotype was significantly higher among cases when compared to controls (P = 0.035) with individuals with the II genotype having greater risk for contracting the COVID-19 disease: OR = 2.074, P = 0.048 in the multivariate analysis. As for disease severity, the DD genotype and D allele were associated with increased risk for developing severe symptoms (OR = 2.845, P = 0.026 and OR = 2.359, P = 0.014, respectively), and the DD genotype with necessitating hospitalization (OR = 2.307, P = 0.042). In parallel, D allele carriers showed a significantly increased risk for developing hypoxia: OR = 4.374, P = 0.045.Conclusion: We found a positive association between ACE1 I and the risk of contracting the COVID-19 disease, and between ACE1 D and a worse outcome of the COVID-19 infection. Therefore, genotyping for ACE1 I/D polymorphism could be used to assess risk and predict severity for better prognosis and management of the disease.

Madura foot, relatively easy to diagnose in tropical countries, is very rare and unrecognized in Morocco, causing diagnostic delays. We present the case of a 54-year-old patient with mycetoma for 3 years who initially consulted two general practitioners, then an endocrinologist and finally a dermatologist in order to be diagnosed correctly. The diagnosis of mycetoma based on biological criteria was established at a late stage of irreversible bone lesions; requiring amputation by the orthopedic team. Mycetomas are fungal or bacterial. Delays in diagnosis and care are frequent in Morocco. The diagnosis is based on biology; however, radiological examinations are necessary to assess the extension. The initial treatment is medicinal. Surgery takes place in late stages.

The use of ultrasonography in acute and critical care medicine is becoming increasingly common. However, use of an airway ultrasound as an adjunct to determine the type of intervention needed and assess complications is not common practice. We report a 56-year-old male who presented to the Emergency Department of the Sungai Buloh Hospital, Selangor, Malaysia, in 2015 with hoarseness, stridor and impending respiratory failure. A point-of-care ultrasound performed to assess the neck and vocal cords indicated a heterogeneous echogenic mass in the larynx, thus ruling out a cricothyroidotomy. The patient was therefore referred for an emergency tracheostomy. This case highlights the importance of point-of-care airway ultrasonography in the assessment of patients with stridor. This imaging technique not only helps to detect the cause of the stridor, but also to determine the feasibility of a cricothyroidotomy in emergency cases. Keywords: Emergency Medicine; Stridor; Ultrasonography; Airway Management; Tracheostomy; Case Report; Malaysia.

Stylometry has got a lot of interest during these recent years because it solved many authorship problems and disputes that were difficult to handle. Author discrimination consists in checking whether two texts are written by the same author or not. In this investigation, we try to make an author discrimination between the Quran (The holy words and statements of God in the Islamic religion) and the Hadith (statements said by the prophet Muhammad) in a segmental form. In fact, 14 text segments are extracted from the Quran book and 11 text segments are extracted from the Bukhari Hadith. These segments have more or less the same size in terms of words and the medium size is about 2080 words per text segment. The Quran is taken in its entirety, whereas for the Prophet’s statements, we chose only the certified texts of the Bukhari book. That is, four series of experiments are done and commented. The first series of experiments concerns several experiments of authorship attribution using different state of the art features and classifiers, the second series of experiments analyses the different texts by using a new parameter called COST, the third series of experiments consists in an authorship discrimination using the frequency of a particular word (“الذين ” meaning those/who in English) and the fourth series of experiments performs a hierarchical clustering on the 25 text segments, in order to assess the real number of clusters (author styles) and to see if the hypothesis of a unique author is possible. This investigation, which represents the continuation of a previous research work on the same topic [Sayoud 2012-a], has further clarified an old enigma, which was impossible to solve for fourteen centuries: all the results of this investigation show unanimously that the two books should have two different authors. La stylométrie a montré beaucoup d'intérêts durant ces dernières années car elle a résolu beaucoup de problèmes et disputes qui étaient difficiles à manipuler. La discrimination d'auteur consiste à vérifier si deux textes sont écrits par le même auteur ou non. Dans cette étude, nous essayons d'exécuter une discrimination d'auteur entre le Coran (Les mots saints et déclarations de Dieu dans la religion Islamique) et le Hadith (déclarations prononcées par le Prophète Muhammad) sous une forme segmentale. En fait, 14 segments de texte sont extraits du Coran et 11 segments sont extraits du Hadith de Bukhari. Ces segments ont plus ou moins la même taille en terme de mots et la taille moyenne est d'environ 2080 mots par segment. Le Coran est pris entièrement, tandis que pour les déclarations du Prophète, nous avons choisi seulement les textes certifiés du livre de Bukhari. Ainsi, quatre séries d'expériences sont faites et commentées. La première série d'expériences concerne plusieurs expériences d'identification d'auteur utilisant différents classifieurs et caractéristiques de l'état de l'art ; la seconde série d'expériences analyse les différents textes en utilisant un nouveau paramètre appelé COST; la troisième série d'expériences consiste en une discrimination d'auteurs utilisant la fréquence d'un mot particulier ("الذين " signifiant Ceux/ Qui en Français) et la quatrième série d'expériences exécute un regroupement hiérarchique sur les 25 segments de texte, dans le but d'estimer le nombre réel de clusters (Styles d'auteurs) et de voir si l'hypothèse d'un auteur unique est possible. Cette étude, qui représente la suite d'un travail de recherche précédent sur le même sujet (Sayoud 2012a), a clarifié d'avantages une ancienne énigme, qui était impossible de résoudre durant quatorze siècles : en fait, tous les résultats de cette étude montrent que les deux livres devraient avoir deux auteurs différents.

This paper aims to introduce the utilization of hazardous sludge with green-lipped mussel shells as concrete mixture components. The hazardous sludge is a side product of wastewater treatment plant operated in NGCC Priok, while green-lipped mussel shells are side product of community activity in Kalibaru, North Jakarta, Indonesia. Utilization is dedicated to preserve the environment, reducing both hazardous sludge generations from wastewater treatment plant and potential waste from social activities in the coastal area. Three different groups of concretes were prepared. The first group contains normal concretes with W/C ratio of 0.5. Subsequently, the second group contains concretes with dry sludge and mussel as a replacement of fine aggregate at different contents, 5% (C1), 10% (C2), and 15% (C3), with W/C ratio of 0.5. Finally, the last group contains concretes with dry sludge as cement replacement and the green-lipped mussel as fine aggregate replacement at different contents of 5% (C4), 10% (C5), and 15% (C6). The results show that dry sludge and green-lipped mussel provide better results when used as a substitute for fine aggregate rather than as cement replacement. In addition, the rate of strength development of concretes containing waste additions are slow compared to normal concretes.

Ihab Abdel Aziz,1 Mohamed Fawzy Alsoda,2 Tarek Mohamed Elmenofy,1 Mohamed Medhat Sakhsoukh,1 Noha Mohamed Abd el Azim,1 Amr Mahmoud Ahmed,1 Sohaila Ali Abd El-Halim,3 Sherine Salaheldin Hassan Baris,3 Yousef Ahmed Fouad,4 Ayman Mohyieldin Elghonemy,1 Heba Metwally,1 Wael Mohamed El Gendy,1 Raghdaa Ali,2 Yehia Mahmoud Basha,5 Eman Abo ElMaaty Mohamed,6 Wafaa Mohamed Amin,6 Maged Adly Naguib,1 Hazem Abdallah Elnashar1 1Department of Ophthalmology, The Memorial Institute for Ophthalmic Research, Giza, Egypt; 2Department of Pediatrics and Neonatology, Ahmed Maher Teaching Hospital, Cairo, Egypt; 3Department of Pediatrics and Neonatology, Mataria Teaching Hospital, Cairo, Egypt; 4Department of Ophthalmology, Ain Shams University Hospitals, Cairo, Egypt; 5Department of Pediatrics and Neonatology, Damanhour Teaching Hospital, Beheira, Egypt; 6Department of Pediatrics and Neonatology, El-Galaa Teaching Hospital, Cairo, EgyptCorrespondence: Hazem Abdallah Elnashar, Department of Ophthalmology, The Memorial Institute for Ophthalmic Research, Giza, 23314, Egypt, Tel +201227011043, Email Dr.hazemelnashar@gmail.comBackground: Retinopathy of prematurity (ROP) is increasing in incidence in developing nations, including Egypt. Secondary prevention requires timely detection through the development of regional screening guidelines, which should be preceded by large-scale studies to characterize the population at risk.Methods: A prospective, multicentric exploratory study that included five large tertiary institutions in an urban Egyptian setting. All infants born with gestational age (GA) < 37 weeks and/or birth weight (BW) ≤ 2000 grams were screened. More mature and heavier infants with unstable clinical course were also included. The primary outcome measure was the rate of ROP and high-risk disease occurrence in relation to underlying risk factors.Results: Of the 768 eyes (384 screened infants), 347 eyes (45.2%) had stage 1 or higher disease, and 43 eyes (5.6%) had high-risk disease. Eyes with stage 1 or higher ROP and treatment-requiring ROP had a mean (± SD) GA of 33.4 (± 2.6) weeks and 32.8 (± 3.2) weeks, and BW of 1842.3 (± 570.1) grams and 1747.6 ± (676.2) grams, respectively. Treatment-requiring eyes belonged to infants that had significantly lower GA and significantly higher prevalence of co-morbidities than non-treatment-requiring eyes.Conclusion: The incidence of ROP and high-risk disease in an urban Egyptian setting are similar to those in comparable settings elsewhere and locally. This exploratory study supports tailoring local screening criteria for ROP, and may aid the future development of national guidelines.Keywords: retinopathy of prematurity, ROP, screening, plus disease, preterm

Carbonic anhydrase II (CA II) is crucial for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance. It is a pivotal druggable target which is implicated in glaucoma, renal, gastric, and pancreatic carcinomas, as well as in malignant brain tumours. Therefore, to identify new CA II (bovine) inhibitors, the current study was designed to synthesize a library of 20 new triazole-linked hydrazones (6a-t). All compounds were characterized by using spectroscopic techniques such as NMR and mass spectrometry. The in-vitro evaluation resulted in impressive inhibitory capability against CA II with IC 50 values ranging from 9.10 ± 0.26-48.26 ± 1.30 µM. Among all derivatives, compounds 6a, 6b, 6d, 6k-6m, 6q, 6s and 6t exhibited potent inhibitory potential with 6t deemed as the most active inhibitor. Additionally, kinetic study of the hybrid 6t revealed concentration dependent type of inhibition with K i value 7.24 ± 0.0086 µM. Furthermore, molecular docking of 6t correlates well with the kinetic analysis. The in-silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Food insecurity, pollution, and malnutrition are some critical issues tackled by the modern world in the recent era. However, edible mushrooms are nutritionally, economically, and biotechnologically valuable groups of macro fungi. Besides being an essential source of edible food, it is also exploited in pharmacological industries as a potential source of anticancer, antioxidant and immunomodulating agents. Mushrooms are not only a rich nutritional source of functional food all over the world, but also have highly significant bioactive compounds that are considered nutraceuticals, cosmeceuticals, and mycotherapeutics across the globe. However, their cultivation is very low compared to their demand. Its cultivation consents the sustainable management of agro-industrial waste and generates decent income using low inputs. Additionally, the mushroom could also be used for the recirculation of forest waste by acting as a natural decomposer that in turn creates great opportunities for the development of economically miserable developing countries, like Pakistan. Mushroom farming is one of the promising approaches to explore such unwanted agro-waste materials from the environment and ensure food security. Mushroom farming is one of the cheapest sources to overcome the deficiency caused by malnutrition. Interestingly, it supports the local economy by offering more and more livelihood opportunities and significant income sources for local and national trade. The current review article emphasizes the prompt mushroom farming industries in Pakistan that can save lives by providing cheaper nutritional food and rich income sources., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:No reports was provided by NO. No reports a relationship with No that includes:. No has patent NA pending to NA. The authors declare that they have no conflict of interest. Authors Ajmal Khan and Sobia Ahsan Halim are working as associate editor in section “Pharmaceutical Sciences” of this journal. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In the quest for novel therapeutic agents against SARS-CoV-2, the proposed study explores the potential of traditional Omani medicinal plants, focusing on the efficacy of natural ligands against the virus's Spike protein. Among 437 identified medicinal plants across Oman, 47 species that are documented for their traditional use in treating respiratory infections, with 30 species' ligands available were chosen for analysis. Molecular docking was performed using Autodock Vina on these ligands, yielding 406 unique ligands post-duplication removal. The binding affinities of target-ligand complexes were precisely determined, ranking them by interaction strength. This process identified Corilagin, a phytochemical from the Acalypha indica plant (locally known as Aeyan Al Aqrada), as the most promising inhibitor. Subsequent analyses using GROMACS for molecular dynamics simulation confirmed its binding stability and interaction dynamics of the Corilagin-protein complex. The in-vitro studies further validated Corilagin's inhibitory effect on SARS-CoV-2, demonstrating a remarkable 92 % inhibition at 0.5 mM concentration. Dilution studies to ascertain the IC 50 value revealed Corilagin's high potency at a micromolar level (IC 50  = 2.15 ± 0.13 μM), underscoring its potential as a drug candidate for SARS-CoV-2 treatment. These findings highlight the significance of ethnomedicine and in-silico methodologies in drug discovery, offering promising directions for future antiviral research., Competing Interests: All the listed authors have read and approved the submitted manuscript. This manuscript/data, or parts thereof, has not been submitted for possible publication to another journal or that the work has previously been published elsewhere. The present study was performed according to international, national and institutional rules considering animal experiments, clinical studies and biodiversity rights., (© 2024 The Authors.)

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 μM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase ( K i = 3.96 ± 0.0048 μM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

According to the most recent edition of the DSM V, neurocognitive disorder (NCD), formerly referred to as dementia, is a debilitating condition that progressively diminishes quality of life. It impacts both physical and cognitive domains, including memory and aberrant behavior. If usual presentation is uncertain, perfusion, functional, and molecular imaging are useful. Gold standard marker for the diagnosis of Alzheimer's disease (AD) is FDG PET imaging. Recent studies have shown promising results, whereby the cerebral blood flow in arterial spin labeling (ASL) of MRI and the hypometabolism FDG PET both show a consistent regional abnormality. Therefore, ASL MRI imaging carries a potential role in assisting diagnosis of neurocognitive disorder., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate., (© 2024. The Author(s).)

Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD + -dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells. Finding new chemical compounds targeted towards SIRT3 was the primary goal of the current investigation. Virtual screening of ~ 800 compounds using molecular docking techniques yielded 8 active hits with favorable binding affinities and poses. Docking studies verified that the final eight compounds formed stable contacts with the catalytic domain of SIRT3. Those compounds have good pharmacokinetic/dynamic properties and gastrointestinal absorption. Based on excellent pharmacokinetic and pharmacodynamic properties, two compounds (MI-44 and MI-217) were subjected to MD simulation. Upon drug interaction, molecular dynamics simulations demonstrate mild alterations in the structure of proteins and stability. Binding free energy calculations revealed that compounds MI-44 (- 45.61 ± 0.064 kcal/mol) and MI-217 (- 41.65 ± 0.089 kcal/mol) showed the maximum energy, suggesting an intense preference for the SIRT3 catalytic site for attachment. The in-vitro MTT assay on breast cancer cell line (MDA-MB-231) and an apoptotic assay for these potential compounds (MI-44/MI-217) was also performed, with flow cytometry to determine the compound's ability to cause apoptosis in breast cancer cells. The percentage of apoptotic cells (including early and late apoptotic cells) increased from 1.94% in control to 79.37% for MI-44 and 85.37% for MI-217 at 15 μM. Apoptotic cell death was effectively induced by these two compounds in a flow cytometry assay indicating them as a good inhibitor of human SIRT3. Based on our findings, MI-44 and MI-217 merit additional investigation as possible breast cancer therapeutics., (© 2024. The Author(s).)

The study examined the antimicrobial and antioxidant potential of pure Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid (70%) and AKBA loaded nanoparticles as topical polymeric films. The optimized concentration (0.05 % w/v) of pure AKBA, boswellic acid (BA), and AKBA loaded silver nanoparticles were used to study its impact on film characteristics. Carboxymethyl cellulose (CMC), sodium alginate (SA), and gelatin (Ge) composite films were prepared in this study. The polymeric films were evaluated for their biological (antioxidant and antimicrobial activities) and mechanical characteristics such as tensile strength (TS) and elongation (%). Moreover, other parameters including water barrier properties and color attributes of the film were also evaluated. Furthermore, assessments were conducted using analytical techniques like FTIR, XRD, and SEM. Surface analysis revealed that AgNP precipitation led to a few particles in the film structure. Overall, the results indicate a relatively consistent microstructure. Moreover, due to the addition of AKBA, BA, and AgNPs, a significant decrease in TS, moisture content, water solubility, and water vapor permeation was observed. The films transparency also showed a decreasing trend, and the color analysis revealed decreasing yellowness (b*) of the films. Importantly, a significant increase in antioxidant activity against DPPH free radicals and ABTS cations was observed in the CSG films. Additionally, the AgNP-AKBA loaded films displayed significant antifungal activity against C. albicans . Moreover, the molecular docking analysis revealed the inter-molecular interactions between the AKBA, AgNPs, and composite films. The docking results indicate good binding of AKBA and silver nanoparticles with gelatin and carboxymethyl cellulosemolecules. In conclusion, these polymeric films have potential as novel materials with significant antioxidant and antifungal activities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The present article describes the muscle relaxant and antipyretic effects of pentacyclic triterpenes, oleanolic acid ( OA ), ursolic acid ( UA ) and betulinic acid ( BA ) isolated from roots of Diospyros lotus in animal models. The muscle relaxant effects of isolated pentacyclic triterpenes were determined by chimney and inclined plane tests. In the chimney test, pretreatment of pentacyclic triterpenes evoked significant dose dependent influence on muscle coordination. When administered intraperitoneally (i.p.) to mice at 10 mg/kg for 90 min, OA , UA , and BA exhibited muscle relaxant effects of 66.72 %, 60.21 %, and 50.77 %, respectively. Similarly, OA , UA, and BA (at 10 mg/kg) illustrated 65.74 %, 59.84 % and 51.40 % muscle relaxant effects in the inclined plane test. In the antipyretic test, significant amelioration was caused by pretreatment of all compounds in dose dependent manner. OA , UA, and BA (at 5 mg/kg) showed 39.32 %, 34.32 % and 29.99 % anti-hyperthermic effects, respectively 4 h post-treatment, while at 10 mg/kg, OA , UA, and BA exhibited 71.59 %, 60.99 % and 52.44 % impact, respectively. The muscle relaxant effect of benzodiazepines is well known for enhancement of GABA receptors. There may exist a similar mechanism for muscle relaxant effect of pentacyclic triterpenes. The in-silico predicted binding pattern of all the compounds reflects good affinity of compounds with GABA A receptor and COX-2. These results indicate that the muscle relaxant and antipyretic activities of these molecules can be further improved by structural optimization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Authors Ajmal Khan and Sobia Ahsan Halim are working as associate editor in section “Pharmaceutical Sciences” of this journal., (© 2024 The Authors.)

The synthesis of a new series of thiadiazine thiones including 5-(2-hydroxyethyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones ( 1 - 5 ), 5-(2-hydroxypropyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones ( 6 - 8 ), 3,5-dipropyl-1, 3, 5-thiadiazine-2-thione ( 9 ) and (2-(5-alkyl/aryl-6-thioxo-1, 3, 5-thiadiazine-3-yl) alkyl acetate/benzoate) ( 10 - 17 ) was accomplished via one pot reaction. The structures of the synthesized compounds were characterized through NMR and Mass spectrometry. The anti-nociceptive activity of compounds was performed on BALB/C mice by hot plate method, where compounds 3 , 5 (50  μ g/kg), and 8 (50, 100  μ g/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time of 15, 30, and 60 min, while compounds 6 and 16 (100  μ g/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time interval of 15 and 30 min. Compounds 1 , 12-13 , and 15 showed moderate activity. Among the tested hits, compounds 5 (17.3 ± 2.2), 11 (16.2 ± 2.1), and 8 (16.1 ± 2.1) showed significant anti-nociceptive potential. Molecular docking studies on the most active anti-nociceptive hits indicated that the activity might be attributed to the ability of the compounds to target μ-opioid receptor (μOR) effectively. Furthermore, compounds 14 and 11 showed anti-bacterial activity against Pseudomonas aeruginosa and MSRA with MIC of 40.97 and 54.77  μ g/mL, respectively. In addition, the predicted ADMET profile of 5 , 9 , and 11 indicates that these molecules follow the drug-likeness criteria, and their activity can be enhanced through structural optimization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Author Ajmal Khan working as a associate editor in section “Pharmaceutical Sciences” of this journal., (© 2024 The Authors.)

In recent years, polyhydroquinolines have gained much attention due to their widespread applications in medicine, agriculture, industry, etc. Here, we synthesized a series of novel hydrazone-based polyhydroquinoline derivatives via multi-step reactions. These molecules were characterized by modern spectroscopic techniques ( 1 H-NMR, 13 C NMR, and LC-HRMS) and their antibacterial and in vitro α-glucosidase inhibitory activities were assessed. Compound 8 was found to be the most active inhibitor against Listeria monocytogenes NCTC 5348, Bacillus subtilis IM 622, Brevibacillus brevis , and Bacillus subtilis ATCC 6337 with a zone of inhibition of 15.3 ± 0.01, 13.2 ± 0.2, 13.1 ± 0.1, and 12.6 ± 0.3 mm, respectively. Likewise, compound 8 also exhibited the most potent inhibitory potential for α-glucosidase (IC 50 = 5.31 ± 0.25 μM) in vitro , followed by compounds 10 (IC 50 = 6.70 ± 0.38 μM), and 12 (IC 50 = 6.51 ± 0.37 μM). Furthermore, molecular docking and DFT analysis of these compounds showed good agreement with experimental work and the nonlinear optical properties calculated here indicate that these compounds are good candidates for nonlinear optics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques ( 1 H NMR, 13 C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC 50  = 26.3 ± 0.4 μM) and 11 (IC 50  = 28.4 ± 0.5 μM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC 50 values ranging from 35.2 ± 1.1 μM to 64.4 ± 0.3 μM. On the other hand, 5 (IC 50  = 22.0 ± 1.1 μM) and 27 (IC 50  = 31.3 ± 1.3 μM) displayed significant, and 19 (IC 50  = 92.6 ± 0.4 μM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2's spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72-90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein's conformational arrangements. The binding free energy ΔG TOTAL of C3 (-38.0 ± 0.08 kcal/mol) and C6E (-41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2., (© 2024. The Author(s).)

The lumbar plexus provides innervation to the lower limbs and is essential in enabling motor movement and sensation in the lower limbs. Some of its branches also innervate the muscles in the pelvic girdle. Compared to the brachial plexus in the upper limbs, the lumbar plexus appears to garner less recognition among physicians and surgeons. However, it is important to understand the anatomy of the lumbar plexus and its branches along with the innervation they enable, as injury to them can cause plexopathies and pathologies that should be recognised by any treating clinician. Lumbar disc herniation, trauma and entrapment by muscles or hypertrophic ligaments are common causes of lumbar plexus or nerve injuries. A video was produced to demonstrate the examination techniques explained in this article. To provide comprehensive examination of the lower limbs, the sciatic nerve and its branches are also included in the examination video., Competing Interests: Conflict of Interest: None., (© Penerbit Universiti Sains Malaysia, 2024.)

Plasticizers are employed to stabilize films by safeguarding their physical stability and avoiding the degradation of the loaded therapeutic drug during processing and storage. In the present study, the plasticizer effect (glycerol) was studied on bioadhesive films based on sodium alginate (SA), carboxymethyl cellulose (CMC) and gelatin (GE) polymers loaded with amphotericin B (AmB). The main objective of the current study was to assess the morphological, mechanical, thermal, optical, and barrier properties of the films as a function of glycerol (Gly) concentration (0.5-1.5 %) using different techniques such as Scanning Electron Microscope (SEM), Texture analyzer (TA), Differential Scanning Calorimeter (DSC), X-Ray Diffraction (XRD), and Fourier Transforms Infrared Spectroscopy (FTIR). The concentration increase of glycerol resulted in an increase in Water Vapor Permeability (WVP) (0.187-0.334), elongation at break (EAB) (0.88-35.48 %), thickness (0.032-0.065 mm) and moisture level (17.5-41.76 %) whereas opacity, tensile strength (TS) (16.81-0.86 MPa), and young's modulus (YM) (0.194-0.002 MPa) values decreased. Glycerol incorporation in the film-Forming solution decreased the brittleness and fragility of the films. Fourier Transform Infrared (FTIR) spectra showed that intermolecular hydrogen bonding occurred between glycerol and polymers in plasticized films compared to control films. Furthermore, molecular docking was applied to predict the binding interactions betweem AmB, CMC, gelatin, SA and glycerol, which further endorsed the stabilizing effects of glycerol in the complex formation between AmB, CMC, SA, and gelatin. The Findings of the current study demonstrated that this polymeric blend could be used to successfully prepare bioadhesive films with glycerol as a plasticizer., Competing Interests: The authors declare no financial interests/personal relationships which may be considered as potential competing interests., (© 2024 The Authors.)

Theoretical research on the keto-enol tautomerization of 2-(2-Hydroxyphenyl)-1-aza azulene (2HPhAZ) and its thiol-thione (2MPhAZ) analouge has been performed using the density functional B3LYP method with the 6-311 +  + G(2d,2p) basis set in gas and ethanol phases. The findings of the MO computation on the energy scale and the prediction of the frontier molecular orbital (FMO) energies demonstrate that the tautomeric structures exist in a static mixture in the ground state, with the enol and thiol structure being more stable than the keto and thione structures in gas phase. The ethanol solvent causes some reordering of the relative stability of 2HPhAZ and 2MPhAZ conformers. The geometries created at the B3LYP/6-311 +  + G(2d,2p) level of theory were used for NBO analysis. In the tautomerization of 2HPhAZ and its mercapto analogue 2-(2-Mercaptophenyl)-1-azaazulene (2MPhAZ), it has been found that the O(S)-C sigma bond is weak due to n O(S) -> σ* C25-O26(S26) and n O(S) -> σ* C15-N16 delocalization. It is also noted that the resulting p character of the corresponding oxygen (sulfur) natural hybrid orbital (NHO) of σ O(S)-C bond orbital is related to the decreased occupancy of the localized σ O(S)-C orbital in the idealized Lewis structure or the increased occupancy of σ* O(S)-C of the non-Lewis orbital and their subsequent impact on molecular stability and geometry (bond lengths) in gas phase and ethanol. Additionally, the energy of charge transfer decreases as the potential rotamers' Hammett constants (R1-R3 for O(S) atoms) increase. The partial charge distribution on the skeleton atoms demonstrates that the intra- and intermolecular interactions can be significantly influenced by the electrostatic attraction or repulsion between atoms. Lastly, the currently applied NBO-based HB strength indicator enables a fair prediction of the frequency of the proton donor NH stretching mode, but this simple picture is hidden by abundant hype conjugative effects., (© 2024. The Author(s).)

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives ( 1-17 ) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC 50 values from 1.23 ± 0.03 to 73.85 ± 0.61 μM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.

Utilizing multi-target drugs shows great promise as an effective strategy against polygenic diseases characterized by intricate patho-mechanisms, such as ulcers, skin dermatitis, and cancers. The current research centers around the creation of hybrid compounds, connecting dibenzazepine and isoxazole, with the aim of exploring their potential as inhibitors for urease and tyrosinase enzymes. Analogs 6a, 6b, 6d, 6 h-6j, and 6 l demonstrated strong inhibitory potential against tyrosinase enzyme with IC 50 values of 4.32 ± 0.31-12.36 ± 0.48. Whereas analogs 6a, 6c, 6e, 6f, 6h-6m, and 6r exhibited potent inhibitory activities against urease enzyme with IC 50 values of 3.67 ± 0.91-15.60 ± 0.18 μM. Furthermore, compounds 6i, 6n, and 6r showed weak toxic effect in BJ-cell line, whereas the remaining compounds were found non-toxic to normal cell line. The mechanistic studies of potent inhibitors of both the enzymes showed competitive mode of inhibition. Molecular docking was employed to establish the relationship between structure and activity and to elucidate the interaction mechanism. This analysis revealed that the active analogs exhibited crucial interactions with the active site residues of urease and tyrosinase, thus corroborating our experimental results. Hence, the generated derivatives of dibenzazepine-linked isoxazoles present intriguing starting points for further investigations into their potential as inhibitors of urease and tyrosinase, with the potential for future modification and enhancement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a-3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC 50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC 50  = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications., (© 2023. Springer Nature Limited.)

Five stable tautomer and rotamers of the 2-(2-Mercaptophenyl)-1-azaazulene (thiol, thione, R1, R2, and R3) molecules were studied using density functional theory (DFT). The geometries of the studied tautomer and rotamers were fully optimized at the B3LYP/6-31G(d,p) level. Thermodynamic calculations were performed at M06-2X/6-311G++(2d,2p) and ωB97XD/6-311G++(2d,2p) in the gas phase and ethanol solution conditions modeled by the solvation model based on density (SMD). The kinetic constant of tautomer and rotamers conversion was calculated in the temperature range 270-320 K using variational transition state theory (VTST) accompanied by one-dimensional wigner tunneling correction. Energy refinement at CCSD(T)/6-311++G(2d,2p) in the gas phase has been calculated. All the studied DFT methods qualitatively give similar tautomer stability orders in the gas phase. The ethanol solvent causes some reordering of the relative stability of 2-(2-Mercaptophenyl)-1-azaazulene conformers. The transition states for the 2-(2-Mercaptophenyl)-1-azaazulene tautomerization and rotamerization processes were also determined. The reactivity, electric dipole moment, and spectroscopic properties of the studied tautomer and rotamers were computed. The hyper-Rayleigh scattering (β HRS ), and depolarization ratio (DR) exhibited promising optical properties when nonlinear optical properties were calculated., (© 2023. Springer Nature Limited.)

Diabetes mellitus is a metabolic disorder and more than 90% of diabetic patients suffer from type-2 diabetes, which is characterized by hyperglycemia. α-Glucosidase inhibition has become an appropriate approach to tackle high blood glucose levels. The current study was focused on synthesizing coumarin-hydrazone hybrids (7a-i) by using facile chemical reactions. The synthesized compounds were characterized by using 1 H-NMR, 13 C-NMR, and IR. To evaluate their anti-diabetic capability, all of the conjugates were screened for in vitro α-glucosidase inhibitory activity to reveal their therapeutic importance. All of the compounds (except 7b) demonstrated significant enzyme inhibitory potential with IC 50 values ranging between 2.39-57.52 μM, as compared to the standard inhibitor, acarbose (IC 50 = 873.34 ± 1.67 μM). Among them, compound 7c is the most potent α-glucosidase inhibitor (IC 50 = 2.39 ± 0.05 μM). Additionally, molecular docking was employed to scrutinize the binding pattern of active compounds within the α-glucosidase binding site. The in silico analysis reflects that hydrazone moiety is an essential pharmacophore for the binding of compounds with the active site residues of the enzyme. This study demonstrates that compounds 7c and 7f deserve further molecular optimization for potential application in diabetic management., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatment with myrrhanone-B and myrrhanol-B at a dose of 5 and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and the concentration of blood glucose level (BGL) in alloxan (120 mg/kg) induced diabetic mice, which indicates that the compounds possess strong anti-diabetic activities. In the biochemical analysis, these compounds improved an abnormal level of total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL-C) to a normal level and increased the high-density lipoprotein cholesterol level (HDLC). Later, drug target of compounds was predicted through in-silico docking which shows that these compounds nicely fit in the active site of α-glucosidase enzyme and mediates excellent interactions with the catalytic residues, Asp214 and Asp349. The in-silico results were confirmed by in-vitro testing of myrrhanone-B and myrrhanol-B against α-glucosidase where both the compounds exhibited excellent inhibitory potency with IC 50 values of 19.50 ± 0.71, and 16.11 ± 0.69 µM, respectively. Furthermore, mechanistic study was conducted to observe their binding mechanism, which reflect that myrrhanol-B has mixed type of inhibition (ki = 12.33 ± 0.030 µM), while myrrhanone-B demonstrates competitive type of inhibition (ki =14.53 ± 0.040 µM)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In current research, two functional components, i.e. , hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as 1 H NMR, 13 C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments., Competing Interests: There is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Hyperactivity of the urease enzyme induces the pathogenesis of peptic ulcers and gastritis. The identification of new urease inhibitors can reduce the activity of urease. Therefore, in the current study, we have evaluated 28 analogues of triazolothiadiazole and triazolothiadiazine heteroaromatics for their in vitro urease inhibitory efficacy. All the tested compounds displayed a remarkable inhibitory potential ranging from 3.33 to 46.83 μM. Among them, compounds 5k and 5e emerged as lead inhibitors with IC 50 values of 3.33 ± 0.11 and 3.51 ± 0.49 μM, respectively. The potent inhibitory potential of these compounds was ∼6.5-fold higher than that of the marketed drug thiourea (IC 50 = 22.45 ± 0.30 μM). The mechanistic insights from kinetics experiments of the highest potent inhibitors ( 4g , 5e , and 5k ) revealed a competitive type of inhibition with k i values 2.25 ± 0.0028, 3.11 ± 0.0031, and 3.62 ± 0.0034 μM, respectively. In silico modeling was performed to investigate the binding interactions of potent inhibitors with the enzyme active site residues, which strongly supported our experimental results. Furthermore, ADME analysis also showed good druglikeness properties demonstrating the potential of these compounds to be developed as lead antiurease agents., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Aim: This study aimed to assess the seroprevalence of SARS-CoV-2 and disease symptoms in Malakand, Pakistan., Materials & Method: 623 samples with suspected SARS-CoV-2 were collected from different regions of Malakand and analyzed to detect SARS-CoV-2 IgG antibodies using ELISA., Results: 306 (49.1%) 0 f 623 patients were anti-SARS-CoV-2 IgG reactive, with a higher prevalence in males (75%) than females (25%). In this study, we enrolled two groups, subjects working in a non-medical setting and subjects working in a medical setting. Clinical symptoms were statistically linked with SARS-CoV-2. Four weeks of follow-up analysis of IgG titers in health care workers showed an increase in IgG antibodies titer., Conclusion: This study gives insights into the community-based spread of SARS-CoV-2 infection, associated immunity, and herd immunity in the studied population. This study can provide insights to the government about early vaccination of this population as most of the population is not yet vaccinated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. The fluorescent spot test (FST) is the conventional method for screening neonates for G6PD. However, it has limitations and quantitative assays such as the CareStart Biosensor 1 are being increasingly recommended. This study aimed to compare FST and CareStart Bioensor 1 in their ability to detect G6PD levels in neonates., Methods: This cross-sectional study involved 455 neonates between June and December 2020. Two milliliters of cord blood were analyzed with CareStart Biosensor 1 and dried cord blood spots with FST. Data was recorded and statistically analyzed. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to determine the performance of FST at specific G6PD cut-off values; Cohen's kappa analysis assessed the agreement between the two methods., Results: The sensitivity of FST at 30% cut-off G6PD activity level was 91.0%, (95% CI: 57.0-100) and specificity of 97.0% (95% CI: 95.0-98.0). At 60% cut-off, the FST sensitivity sharply declined to 29.0% (95% CI: 19.0-40.0) with a specificity of 100% (95% CI: 98.0-100). The overall prevalence of G6PD deficiency was 5.1% as measured by FST and 17.8% by Biosensor 1 ( p < 0.001)., Conclusions: In this study, FST missed a significant proportion of cases of intermediate G6PD levels. FST also misclassified several G6PD intermediate individuals as normal, rendering them susceptible to oxidative stress. Biosensor 1 reported a significantly higher prevalence of G6PD deficiency., (Copyright © 2023, Oman Medical Journal.)

A series of novel alkyl derivatives ( 2-5a,b ) and 1 H -1,2,3-triazole analogues ( 7a-k ) of Meldrum's acid were synthesized in a highly effective way by using "click" chemistry and screened for in vitro α -glucosidase inhibitory activity to examine their antidiabetic potential. 1 H NMR, 13 C-NMR, and high-resolution electrospray ionization mass spectra (HR-ESI-MS) were used to analyze each of the newly synthesized compounds. Interestingly, these compounds demonstrated high to moderate α-glucosidase inhibitory potency having an IC 50 range of 4.63-80.21 μM. Among these derivatives, compound 7i showed extraordinary inhibitory activity and was discovered to be several times more potent than the parent compound Meldrum ( 1 ) and the standard drug acarbose. Later, molecular docking was performed to understand the binding mode and the binding strength of all the compounds with the target enzyme, which revealed that all compounds are well fitted in the active site of α -glucosidase. To further ascertain the structure of compounds, suitable X-ray single crystals of compounds 5a , 7a , and 7h were developed and studied. The current investigation has shown that combining 1 H -1,2,3-triazole with the Meldrum moiety is beneficial. Furthermore, this is the first time that the aforementioned activity of these compounds has been reported., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Hepatitis C virus (HCV) is one of the most prevalent pathogens which causes significant morbidity and mortality in 2% of the world's population. Several interferon-stimulated genes (ISGs) are involved in HCV clearance by interacting with the viral proteins. Among these ISGs, the tripartite motif (TRIM) family genes are elevated during HCV infection. This study aims to evaluate the expression of three TRIM family genes in chronic hepatitis C patients, distributed among different groups, including TRIM11, TRIM14, and TRIM25. A total of 242 participants were recruited in this study, including 182 infected patients, 37 naïve individuals, and 23 control individuals. Out of 182 infected patients, 100 achieved sustained virologic response (SVR), 61 achieved rapid virologic response (RVR), and 21 patients developed hepatocellular carcinoma (HCC), showing no response to the given treatments. Our results indicate highest expression levels of TRIM mRNA transcripts in the RVR group with the highest increase of 7.5 folds in TRIM25, 6.68 folds in TRIM14, followed by the data from patients of the SVR group. The elevation was also evident in other groups, i.e., SVR and HCC, in different patterns among all the three TRIM genes. In addition to elevation in expression levels, a linear correlation is observed between the TRIM mRNAs and viral loads of HCV. These results showed the potential role of TRIM family genes in HCV restriction., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Central nervous system (CNS) toxoplasmosis is an opportunistic infection caused by the intracellular protozoan parasite Toxoplasma gondii . This organism typically causes disease in immunocompromised patients with human immunodeficiency virus (HIV). We reported a case of a 52-year-old woman with neurology symptoms and Magnetic resonance imaging (MRI) brain shows both eccentric and concentric target signs, which are typical signs in a patient with cerebral toxoplasmosis but rarely displayed in the same lesion. The MRI played a crucial role in diagnosing the patient and distinguishing CNS diseases commonly found in HIV patients. Our objective is to discuss the imaging findings that aided in the patient's diagnosis., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors.)

The tautomerizations mechanism of 4-(methylsulfanyl)-3[(1Z)-1-(2-phenylhydrazinylidene) ethyl] quinoline-2(1H)-one were inspected in the gas phase and ethanol using density function theory (DFT) M06-2X and B3LYP methods. Thermo-kinetic features of different conversion processes were estimated in temperature range 273-333 K using the Transition state theory (TST) accompanied with one dimensional Eckert tunneling correction (1D-Eck). Acidity and basicity were computed as well, and the computational results were compared against the experimental ones. Additionally, NMR, global descriptors, Fukui functions, NBO charges, and electrostatic potential (ESP) were discussed. From thermodynamics analysis, the keto form of 4-(methylsulfanyl)-3-[(1Z)-1-(2 phenylhydrazinylidene) quinoline-2(1H)-one is the most stable form in the gas phase and ethanol and the barrier heights required for tautomerization process were found to be high in the gas phase and ethanol ~ 38.80 and 37.35 kcal/mol, respectively. DFT methods were used for UV-Vis electronic spectra simulation and the time-dependent density functional theory solvation model (TDDFT-SMD) in acetonitrile compounds., (© 2023. The Author(s).)

The fundamental aim of this project was to assess the sonophotocatalytic degradation of textile dyes mostly eluted from industries into wastewater. Such a pretreatment of wastewater makes the water suitable for drinking and irrigation purposes and thereby helps protect the ecosystem. The main objective of this research was to degrade real samples and laboratory-prepared samples sonophotocatalytically using a silver-impregnated ZnO photocatalyst. Reactive dyes, including Fast Yellow AB (FY AB) and Remazol Brilliant Violet-5R (RBV-5R), were degraded via this technique under optimum and enhanced conditions. The photocatalyst was synthesized through a wet impregnation process and characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis, Fourier transform infrared (FTIR) spectroscopy, and UV/vis spectroscopy to examine the morphology, composition, and functional groups of the photocatalyst. Parameters including pH, dosage, dye concentration, scavengers, and effects of oxidizing agents were considered. Under optimal conditions, the degradations were 95.7 and 88.9% for RBV-5R and FY AB, respectively, in 60 min. The pH and oxidizing agents played important roles in the degradation process. Only 43.8 and 32.5% of RBV-5R and FY AB, respectively, were degraded in the absence of an oxidizing agent. With the addition of oxidizing agents, 95.7 and 88.9% of RBV-5R and FY AB degradation occurred, respectively. The optimal pH values for RBV 5-R and FY-AB were 8 and 12, respectively. A comparison between the photocatalytic and sonophotocatalytic processes revealed degradation efficiencies of 41 and 33% for RBV-5R and FY-AB, respectively, by the photocatalytic process. Therefore, results indicate the productivity of the sonophotocatalytic degradation process., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This scoping review aimed to summarize the effects of natural products targeting phosphoinositide-3-kinases/serine/threonine kinase (PI3K/AKT) in myocardial ischemia-reperfusion injury (MIRI). The review details various types of natural compounds such as gypenoside (GP), gypenoside XVII (GP-17), geniposide, berberine, dihydroquercetin (DHQ), and tilianin which identified to reduce MIRI in vitro and in vivo by regulating the PI3K/AKT signaling pathway. In this study, 14 research publications that met the inclusion criteria and exclusion criteria were shortlisted. Following the intervention, we discovered that natural products effectively improved cardiac functions through regulation of antioxidant status, down-regulation of Bax, and up-regulation of Bcl-2 and caspases cleavage. Furthermore, although comparing outcomes can be challenging due to the heterogeneity in the study model, the results we assembled here were consistent, giving us confidence in the intervention's efficacy. We also discussed if MIRI is associated with multiple pathological condition such as oxidative stress, ERS, mitochondrial injury, inflammation, and apoptosis. This brief review provides evidence to support the huge potential of natural products used in the treatment of MIRI due to their various biological activities and drug-like properties.

Background/aims: Macrophages interact with tumor cells within the tumor microenvironment (TME), which plays a crucial role in tumor progression. Cancer cells also can instruct macrophages to facilitate the spread of cancer and the growth of tumors. Thus, modulating macrophages-cancer cells interaction in the TME may be therapeutically beneficial. Although calcitriol (an active form of vitamin D) has anticancer properties, its role in TME is unclear. This study examined the role of calcitriol in the regulation of macrophages and cancer cells in the TME and its influence on the proliferation of breast cancer cells., Methods: We modeled the TME, in vitro, by collecting conditioned medium from cancer cells (CCM) and macrophages (MCM) and culturing each cell type separately with and without (control) a high-dose (0.5 µM) calcitriol (an active form of vitamin D). An MTT assay was used to examine cell viability. Apoptosis was detected using FITC (fluorescein isothiocyanate) annexin V apoptosis detection kit. Western blotting was used to separate and identify proteins. Quantitative real-time PCR was used to analyze gene expression. Molecular docking studies were performed to evaluate the binding type and interactions of calcitriol to the GLUT1 and mTORC1 ligand-binding sites., Results: Calcitriol treatment suppressed the expression of genes and proteins implicated in glycolysis (GLUT1, HKII, LDHA), promoted cancer cell apoptosis, and reduced viability and Cyclin D1gene expression in MCM-induced breast cancer cells. Additionally, calcitriol treatment suppressed mTOR activation in MCM-induced breast cancer cells. Molecular docking studies further showed efficient binding of calcitriol with GLUT1 and mTORC1. Calcitriol also inhibited CCM-mediated induction of CD206 and increased TNFα gene expression in THP1-derived macrophages., Conclusion: The results suggest that calcitriol may impact breast cancer progression by inhibiting glycolysis and M2 macrophage polarization via regulating mTOR activation in the TME and warrants further investigation in vivo., Competing Interests: The authors do not have any conflict of interests., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background and Objective: The current coronavirus disease-2019 (COVID-19) pandemic has triggered a worldwide health and economic crisis. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the disease and completes its life cycle using the RNA-dependent RNA-polymerase (RdRp) enzyme, a prominent target for antivirals. In this study, we have computationally screened ∼690 million compounds from the ZINC20 database and 11,698 small molecule inhibitors from DrugBank to find existing and novel non-nucleoside inhibitors for SARS-CoV-2 RdRp., Methods: Herein, a combination of the structure-based pharmacophore modeling and hybrid virtual screening methods, including per-residue energy decomposition-based pharmacophore screening, molecular docking, pharmacokinetics, and toxicity evaluation were employed to retrieve novel as well as existing RdRp non-nucleoside inhibitors from large chemical databases. Besides, molecular dynamics simulation and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) method were used to investigate the binding stability and calculate the binding free energy of RdRp-inhibitor complexes., Results: Based on docking scores and significant binding interactions with crucial residues (Lys553, Arg557, Lys623, Cys815, and Ser816) in the RNA binding site of RdRp, three existing drugs, ZINC285540154, ZINC98208626, ZINC28467879, and five compounds from ZINC20 (ZINC739681614, ZINC1166211307, ZINC611516532, ZINC1602963057, and ZINC1398350200) were selected, and the conformational stability of RdRp due to their binding was confirmed through molecular dynamics simulation. The free energy calculations revealed these compounds possess strong binding affinities for RdRp. In addition, these novel inhibitors exhibited drug-like features, good absorption, distribution, metabolism, and excretion profile and were found to be non-toxic., Conclusion: The compounds identified in the study by multifold computational strategy can be validated in vitro as potential non-nucleoside inhibitors of SARS-CoV-2 RdRp and holds promise for the discovery of novel drugs against COVID-19 in future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The dorsal column medial lemniscus (DCML) system is a sensory pathway of the central nervous system; it carries sensations of soft touch, vibration, proprioception, two-point discrimination, and pressure from the skin and joints. The clinical signs of the DCML pathway lesions include loss of soft touch, vibratory sense, proprioception, discrimination sense, and a positive Rhomberg test. Diseases that affect this pathway are usually degenerative, for example, spinal cord degeneration due to vitamin B12 deficiency; it can also be affected by trauma or infarction of the posterior spinal artery causing posterior cord syndrome. This video manuscript provides a step-by-step examination technique of the dorsal column examination, specially catered for Malaysian medical students and trainees. A series of videos show the techniques for soft touch sensation examination, examination of the vibratory sense, examination of the joint position sense, examination of two-point discrimination and the Rhomberg test. We hope that students can adhere to these techniques and apply them in their daily neurological assessments., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2023.)

Phthalimides have diverse bioactivities and are attractive molecules for drug discovery and development. Here, we explored new synthesized phthalimide derivatives (compounds 1 - 3 ) in improving memory impairment associated with Alzheimer's disease (AD), using in vitro and ex vivo acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition and in vivo models, including Y-maze test and novel object recognition test (NORT). Compounds 1 - 3 exhibited significant AChE activity with IC 50 values of 10, 140, and 18 μM and BuChE with IC 50 values of 80, 50, and 11 μM, respectively. All compounds 1 - 3 showed excellent antioxidant potential in DPPH and ABTS assays with IC 50 values in the range of 105-340 and 205-350 μM, respectively. In ex vivo studies, compounds 1 - 3 also significantly inhibited both enzymes in a concentration-dependent manner along with significant antioxidant activities. In in vivo studies, compounds 1 - 3 reversed scopolamine-induced amnesia as indicated by a significant increase in the spontaneous alternation in the Y-maze test and an increase in the discrimination index in the NORT. Molecular docking was also conducted for compounds 1 - 3 against AChE and BuChE, which showed that compounds 1 and 3 have excellent binding with AChE and BuChE as compared to 2 . These findings suggest that compounds 1 - 3 possess significant antiamnesic potential and may serve as useful leads to develop novel therapeutics for the symptomatic management and treatment of AD., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Polyhydroquinoline derivatives ( 1-15 ) were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds ( 1-15 ) were deduced through different spectroscopic techniques such as 1 H NMR, 13 C NMR, and HR-ESI-MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds 11 (IC 50 = 0.56 ± 0.01 μM), 10 (IC 50 = 0.94 ± 0.01 μM), 4 (IC 50 = 1.47 ± 0.01 μM), 2 (IC 50 = 2.20 ± 0.03 μM), 6 (IC 50 = 2.20 ± 0.03 μM), 12 (IC 50 = 2.22 ± 0.07 μM), 7 (IC 50 = 2.76 ± 0.04 μM), 9 (IC 50 = 2.78 ± 0.03 μM), and 3 (IC 50 = 2.88 ± 0.05 μM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds ( 8 , 5 , 14 , 15 , and 13 ) showed significant α-glucosidase inhibitory potential with IC 50 values of 3.13 ± 0.10, 3.34 ± 0.06, 4.27 ± 0.13, 6.34 ± 0.15, and 21.37 ± 0.61 μM, respectively. Among the synthesized series, two compounds, i.e., 11 and 10 , showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug "acarbose" (IC 50 = 873.34 ± 1.67 μM). An in silico method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our in silico observation complements with the experimental results., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)