Narra J (Journal)
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    A novel diastolic dysfunction score: A proposed diagnostic predictor for left ventricular dysfunction in obese population

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    Obesity-related diastolic dysfunction is an emerging contributor to heart failure and cardiovascular mortality. However, effective and accessible diagnostic tools are still limited. Current methods for assessing diastolic dysfunction are often invasive or technologically demanding, making them impractical for routine clinical use and community settings. The aim of this study was to develop a novel, non-invasive scoring system designed to predict diastolic dysfunction in obese adults, addressing this diagnostic gap. This community-based, prospective cross-sectional study was conducted in Jakarta, Indonesia, from March to November 2021, and included 82 participants aged 18 to 60 years, all with a body mass index (BMI) ≥25 kg/m². Patients with acute or critical illnesses, valvular heart diseases, or acute confusional states were excluded. Each participant underwent blood tests, polysomnography, and echocardiography. Of the study population, 80.5% were diagnosed with obstructive sleep apnea (OSA), and 12.2% exhibited diastolic dysfunction, all within the OSA group. The novel scoring system integrates four predictors: oxygen desaturation index (ODI) ≥39 (score 1; prevalence ratio: 4.31 (95% confidence interval (CI): 1.58–11.75)), HbA1C ≥5.95% (score 2; prevalence ratio: 6.32 (95%CI: 2.84–14.06)), pulmonary artery wedge pressure (PAWP) ≥10 mmHg (score 1; prevalence ratio: 5.95 (95%CI: 2.30–15.39)), and global longitudinal strain (GLS) ≥-16.95% (score 1; prevalence ratio: 4.32 (95%CI: 1.87–9.99)). A score of ≥2 predicted diastolic dysfunction with 90% sensitivity, with positive predictive value and negative predictive value of 40.91% and 98.33%, respectively. In conclusion, the diastolic dysfunction score is a simple and practical tool for the early detection of diastolic dysfunction in obese individuals without cardiovascular symptoms

    Prevalence and risk factors of adult attention deficit hyperactivity disorder in university students: A study from the United Arab Emirates

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    Attention deficit hyperactivity disorder (ADHD), once considered primarily a childhood condition, is now increasingly recognized as a disorder that persists into adulthood and significantly impacts academic and professional success. The aim of this study was to investigate the prevalence of ADHD and identify associated risk factors among university students. A cross-sectional study was conducted over a period of six months at Ras Al Khaimah Medical and Health Sciences University, United Arab Emirates. Data were collected through a self-report questionnaire addressing sociodemographic, lifestyle, and family environment factors. ADHD symptoms were assessed using the World Health Organization Adult ADHD Self-Report Scale version 1.1, based on the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition criteria. The study sample included 472 students, with a mean age of 19.9±1.85 years. The overall prevalence of ADHD was 13.6% (n=64). Logistic regression analysis revealed significant associations between the mother's smoking status (odds ratio (OR): 2.35; 95% confidence interval (95%CI): 1.949–5.862, p=0.050) and living in shared housing (OR: 3.35; 95%CI: 1.674–6.723, p=0.001) with increased odds of ADHD. Conversely, being male (OR: 0.4; 95%CI: 0.216–0.891, p=0.02) and being born full-term (OR: 0.331; 95%CI: 0.138–0.794, p=0.013) were associated with decreased odds of ADHD. Other factors, such as college affiliation, smoking status, exercise habits, maternal employment, mode of delivery, and pregnancy complications, were not significant risk factors. These findings highlight the need for targeted interventions in university settings, including early screening, tailored support services, and increased staff awareness, to support students with ADHD and enhance their academic success and well-being

    Dual effects of Camellia sinensis and Andrographis paniculata on hyperglycemia and infection in Drosophila

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    The coexistence of hyperglycemia and infectious diseases represents a critical global health challenge, particularly in resource-limited settings where it amplifies disease severity and complicates treatment approaches. Medicinal plants such as Camellia sinensis and Andrographis paniculata have gained recognition for their antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for addressing this double health burden. The aim of this study was to establish a preclinical model of hyperglycemia and infection (HI model) using Drosophila melanogaster and to investigate the therapeutic potential of C. sinensis and A. paniculata extracts in alleviating the burden associated with the HI condition. In this study, the HI model was established by simultaneously exposing D. melanogaster larvae to a high-concentration sucrose solution and Staphylococcus aureus for 24 hours. The larvae were then transferred to a high-sucrose diet supplemented with C. sinensis or A. paniculata extracts. Survival assays and molecular analyses were subsequently performed to evaluate the outcomes. Our findings revealed that the combination of hyperglycemia and infection significantly reduced survival rates in the Drosophila model. However, treatment with 1.25% C. sinensis and A. paniculata extracts notably improved survival, attributed to their antibacterial activity and regulation of key molecular pathways involved in immune responses, metabolic balance, and endogenous antioxidant defenses. These findings validate the utility of D. melanogaster as a model organism for investigating the double burden of HI. Furthermore, the study offers compelling evidence of the dual therapeutic potential of C. sinensis and A. paniculata in mitigating the detrimental effects of this condition. Overall, this research underscores the significant promise of plant-derived compounds in managing HI and paves the way for future studies to explore their underlying mechanisms and potential clinical applications

    Effect of the modified Atkins diet on NLRP3, caspase-1, IL-1β, and IL-10 in patients with tetralogy of Fallot undergoing open-heart surgery: A randomized controlled trial

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    Cardiopulmonary bypass in tetralogy of Fallot (TOF) corrective surgery induces hyperinflammation by activating NLRP3, caspase-1, and interleukin-1β (IL-1β), subsequently triggering an interleukin-10 (IL-10) response. Despite its known metabolic and anti-inflammatory effects, the impact of the modified Atkins diet (MAD) in pediatric cardiac surgery remains unexplored, with no studies on its use in TOF patients undergoing open-heart surgery. The aim of this study was to assess the effect of MAD on the expression of NLRP3, caspase-1, IL-1β, and IL-10, in TOF patients undergoing open-heart surgery. A double-arm, randomized-controlled trial was conducted with 44 TOF patients. The treatment group (n=22) received the MAD, a low-carbohydrate, high-fat regimen with unrestricted fat and protein intake for at least 14 days preoperatively, while the control group (n=22) followed a standard diet without carbohydrate restriction. Blood plasma and infundibulum heart tissues were collected for analysis. Whole blood samples were collected using a winged infusion needle before the intervention, an Abbocath infusion needle after 14 days of intervention, and a syringe without a needle connected to an arterial line in patients undergoing open-heart surgery at 6, 24, and 48 hours post-surgical correction. Infundibulum heart tissues were collected during the open-heart surgery. This study demonstrated significant differences in NLRP3 protein expression (p=0.015), caspase-1 protein expression (p=0.001), and IL-10 levels between before intervention and 6-, 24-, and 48-hours post-surgery in the MAD group compared to the control group. In contrast, no significant differences in IL-10 levels were observed in the control group between before intervention and 48 hours post-surgery (p=0.654). In conclusion, MAD may modulate perioperative inflammation in TOF patients undergoing open-heart surgery by downregulating NLRP3 and caspase-1 expression while sustaining IL-10 levels. Despite reduced NLRP3 and caspase-1 expression, unchanged IL-1β levels indicate alternative regulatory mechanisms

    Network pharmacology, molecular docking, and molecular dynamics analyses to explore the molecular mechanism of paclitaxel in atherosclerosis therapy

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    Atherosclerosis is a chronic arterial disease and the leading cause of vascular death. Paclitaxel has long been recognized as an anticancer agent, but recent studies have shown that paclitaxel can also potentially reduce the progression of atherosclerosis. The aim of this study was to explore the molecular mechanism of paclitaxel as an atherosclerosis therapy using in silico study. Pharmacokinetic and pharmacodynamic analyses of paclitaxel were conducted using SwissADME, ProTox v3.0, and SCFbio websites. Cytoscape software was used to construct a network of protein-protein interactions, and the key proteins involved in paclitaxel-related atherosclerosis were identified, including AKT serine/threonine kinase 1 (AKT1), Jun N-terminal kinase (JNK), and Endothelin 1 (ET1). These key proteins were then subjected to molecular docking and molecular dynamic simulation using MOE and Yasara applications. Pharmacokinetic and pharmacodynamic analyses revealed that paclitaxel has good distribution, metabolism, and excretion properties. However, paclitaxel has shortcomings in absorption, toxicity, and water solubility. According to the results of molecular docking, paclitaxel showed consistent results as the most potential inhibitor of AKT1 (-9.59 kcal/mol), ET1 (-9.16 kcal/mol), JNK (-8.72 kcal/mol) when compared to the control ligands. Molecular dynamics simulations also confirmed the interaction stability between paclitaxel with AKT1, ET1, and JNK, with paclitaxel-AKT1 demonstrating the highest conformational stability (Carbon-α Root Mean Square Deviation <3.0 Å). Even though our in-silico results are promising, more experimental studies are required to confirm the efficacy of paclitaxel as an atherosclerosis therapy

    Developing a maturity-level model for interprofessional collaboration in elective surgery preparation

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    Interprofessional collaboration plays a crucial role in the preparation for elective surgeries to enhance the quality, safety, and efficiency of patient care. However, its implementation continues to encounter substantial obstacles, which require the creation of a customized maturity model to effectively resolve these concerns. The aim of this study was to develop an interprofessional collaboration maturity model that is specifically designed for the context of elective surgery preparation. This qualitative study employed a case study approach, conducted in 2024. This maturity model was developed through four stages: (1) a literature study to identify key interprofessional collaboration indicators in surgery; (2) in-depth interviews with ten healthcare professionals at Universitas Muhammadiyah Malang Hospital, Malang, Indonesia; (3) adaptation of existing maturity models (Fleming, Hudson, collaboration maturity model, and quality management system) as a framework for synthesizing data from the findings of stage 2 (in-depth interviews); and (4) expert panel review to evaluate the maturity model. We successfully developed an interprofessional collaboration maturity model specifically applied to elective surgery preparation, Preoperative Interprofessional Collaboration Maturity Model (P-ICMM), consisting of five maturity levels: emerging, developing, coordinated, integrated, and optimized. Each level’s assessment criteria are based on indicators of interprofessional collaboration. This maturity model has been evaluated by the experts in elective surgery preparation to ensure its validity and applicability. This maturity model is expected to help hospitals identify the level of interprofessional collaboration, design strategies to enhance collaboration, and ultimately improve the quality of healthcare services and patient safety in the preparation for elective surgeries

    Design of lipid nanoparticle (LNP) containing genetic material CRISPR/Cas9 for familial hypercholesterolemia

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    Familial hypercholesterolemia is a genetic disorder caused by mutations in the low-density lipoprotein receptor gene (LDLR) and the current treatment still focuses on symptom management. The aim of this study was to develop a lipid nanoparticle (LNP)-based delivery system for the CRISPR/Cas9 component in correcting LDLR gene mutations. LNPs were prepared using an ultrasonic-solvent emulsification technique by varying the surfactant: oil ratio (SOR), homogenization speed and time, and sonication time. Next, the LNP surface was modified by adding DSPE-PEG2000-NH2 and polyethyleneimine. The next stage is to design the single guide RNA (sgRNA) and Donor DNA wildtype (Donor DNA wt). This genetic material was complexed with LNP and then transfected into Hepa1-6 LDLR mt cells, an in vitro representation of cells suffering from familial hypercholesterolemia. This optimization process produced LNPs with a particle size of 118.6±0.8 nm and a polydispersity index of 0.34±0.03. The LNP surface modification resulted in a zeta potential of +7.5 mV. A transmission electron microscope (TEM) analysis howed spherical morphology with size distribution following a regular pattern. LNP cell viability tests showed good biocompatibility at concentrations <15 mM with a half-maximal inhibitory concentration (IC50) value of 27.7 mM. The dominant cellular uptake mechanism of LNP was through the clathrin-mediated endocytosis (CME) pathway. The Hepa1-6 LDLR mt cell model was successfully produced with the transfecting agent Lipofectamine 3000 by homology-directed repair (HDR) mechanism. The LNP-genetic material complex with a ratio of sgRNA:Cas9:Donor DNA wt (1:1:0.04) showed an increase in LDLR gene expression of 3.3±0.2 times and LDLR protein levels reached 12.95±0.25 ng/mL on day 4 after transfection. The results of this study indicate that the developed LNP-based delivery system has the potential for gene therapy applications in familial hypercholesterolemia

    Thymoquinone and madecassoside improve motor function in a rotenone-induced mouse model of early Parkinson’s disease: Role of dopamine, alpha-synuclein and mBDNF

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    Parkinson’s disease is a progressive, incurable neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and pathological aggregation of α-synuclein in the midbrain, leading to motor dysfunction. Thymoquinone (TQ), an active compound from Nigella sativa, has demonstrated antioxidant properties that may reduce dopamine degradation, while madecassoside (MA), a triterpenoid component of Centella asiatica, exhibits neuroprotective effects. To date, no study has investigated the combined effects of TQ and MA in a Parkinson’s disease model. The aim of this study was to evaluate the synergistic neuroprotective potential of TQ and MA on motor function, dopamine levels, α-synuclein accumulation, and mature brain-derived neurotrophic factor (mBDNF) expression in a rotenone (ROT)-induced mouse model of early Parkinson’s disease. Rotenone (2.5 mg/kg BW) was administered subcutaneously for two weeks to induce Parkinson’s disease, while TQ alone, MA alone and combination of TQ and MA at various doses, as well as a reference drug (pramipexole) were given every 48 hours concurrently with rotenone. Motor symptoms were assessed through behavioral tests, including the open field test (OFT), beam walking test, and hanging wire test; midbrain dopamine levels were quantified via enzyme-linked immunosorbent assay (ELISA), α-synuclein expression was assessed using Western blotting, and immunohistochemistry was used to detect mBDNF-positive cells in the cerebral cortex. The combination of TQ and MA significantly increased midbrain dopamine levels and improved locomotor activity, as shown by increased total distance traveled and mean velocity in ROT-induced mice. Biochemically, this combined treatment reduced α-synuclein expression, suggesting attenuation of early pathological aggregation typically observed in Parkinson’s disease. Although the increase in mBDNF expression in the cerebral cortex was not statistically significant, it was higher in the TQ-MA treatment group compared to controls and other groups. Collectively, these results highlight the therapeutic potential of TQ and MA in combination to counteract both motor deficits and early neurochemical disruptions in a ROT-induced model of Parkinson’s disease

    Lichen substances from Teloschistes flavicans (Sw.) Norman: Isolation, crystal structure, and evaluation of their antibacterial activities

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    Teloschistes flavicans (Sw.) Norman is a lichen known as the golden-haired lichen. This lichen has been recognized and used in herbal medicine mixtures as an antimicrobial and bioindicator of air pollution that plays a role in ecological systems. The aim of this study was to explore the potential of its secondary metabolites as antibacterial and anticancer agents, particularly against bacterial pneumonia. Two main compounds (vicacinin and parietin) were isolated with chromatography and identified by spectrometry and single-crystal X-ray diffraction. The crystallographic data of vicanicin are reported for the first time. Chromatography and recrystallization methods were used to obtain both compounds with orange (parietin) and white (vicanicin) crystals. Furthermore, these compounds were evaluated for cytotoxicity on keratinocytes (HaCaT) cells and antibacterial activity against pneumonia pathogens (Klebsiella pneumoniae ATCC 1706, Streptococcus pneumoniae ATCC 49619, Moraxella catarhalis ATCC 25240, and Staphylococcus pyogenes ATCC 19615). The cytotoxic activity of these compounds was moderate at the concentration of 50-100 µM. The antibacterial pneumonia activity was relatively weak compared to chloramphenicol. Between the two compounds, vicanicin showed stronger activity than parietin against all strains. Vicanicin was more active against Klebsiella pneumoniae and Staphylococcus pyogenes with minimum inhibitory concentrations of 156±0.77 µM and 156±0.91 µM, respectively. In this study, comprehensive molecular structures of parietin and vicanicin have been successfully elucidated, and their antibacterial and cytotoxic activities have been provided

    Exploring the potential of Laportea decumana extract compounds as COX-1 and COX-2 inhibitors: An in silico study

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    Laportea decumana (Roxb.) Wedd., known as itchy leaves, is traditionally used for pain relief due to its bioactive compounds. However, previous studies were limited by resource-intensive in vivo methods and a lack of mechanistic insights into cyclooxygenase (COX)-1 and COX-2 binding. The aim of this study was to identify compounds in the n-hexane and ethyl acetate extracts of L. decumana with potential as COX-1 and COX-2 inhibitors and to predict their binding affinity and stability within the binding pocket through molecular dynamics simulations. Leaves collected from Arso, Keerom Regency, Papua, Indonesia, were dried, sieved into simplicia, and macerated with n-hexane to obtain a n-hexane extract. The residual simplicia was further macerated with ethyl acetate to produce an ethyl acetate extract. N-hexane extract compounds were analyzed by gas chromatography-mass spectrometry (GC-MS), and ethyl acetate extract compounds by liquid chromatography-mass spectrometry (LC-MS). Identified chemicals were used in in silico evaluations targeting COX-1 and COX-2. This study identified ten compounds with high performance in docking analysis, which were further evaluated by molecular dynamics. The n-hexane extract contained 31 compounds, while the ethyl acetate extract contained 27. Among these, 4,8,12,16-tetramethylheptadecan-4-olide from the n-hexane extract demonstrated the strongest affinity for both COX-1 and COX-2, with binding free energies of -41.62±1.03 kcal/mol and -33.05±0.11 kcal/mol, respectively. Its interactions were comparable to those of native ligands, with superior binding free energy. In the ethyl acetate extract, pseudosantonim demonstrated the highest affinity for COX-1 (-24.41±1.32 kcal/mol), while arteamisinine showed strong potential as a COX-2 inhibitor (-23.53±0.30 kcal/mol). In conclusion, 4,8,12,16-tetramethylheptadecan-4-olide was the most potent COX-1 and COX-2 inhibitor, pseudosantonim was the most effective COX-1 inhibitor, and arteamisinine demonstrated COX-2 inhibitory potential. Further validation through in vitro or in vivo studies is recommended

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