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Plant-based synthesis of gold and silver nanoparticles using Artocarpus heterophyllus aqueous leaf extract and its anticancer activities
Green synthesis of nanoparticles has garnered significant attention for its sustainable and environmentally friendly approach. Despite extensive research on Artocarpus heterophyllus-derived nanoparticles using seeds, fruits, and rind, the therapeutic potential of its leaf extract remains largely unexplored, particularly in MCF-7 breast cancer cells. The aim of this study was to investigate the potential of aqueous leaf extract from A. heterophyllus as a reducing and capping agent to synthesize silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), as well as to evaluate their anticancer efficacy. The nanoparticles were characterized using ultraviolet-visible spectroscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and particle size analysis to confirm the formation. To evaluate anticancer potential, key oncogenes associated with cancer proliferation and survival were analyzed, including c-Myc, cyclin D1, human epidermal growth factor receptor-2 (HER-2), microRNA-622 (miR-622), and cyclooxygenase-2 (COX-2). The present study demonstrated that AgNPs and AuNPs synthesized from A. heterophyllus extract had distinct sizes and shapes, with AgNPs averaging approximately 12.75 nm and exhibiting a spherical morphology, while AuNPs averaged 109.26 nm and had a pentagonal shape. Furthermore, AuNPs had no anticancer activity. In contrast, AgNPs showed potent anticancer effects, with inhibitory concentration (IC50) values of 124.626 and 54.981 µg/mL at 48 and 72 hours, respectively. The AgNPs treatment increased the proportion of cells in G2/M phase, indicating the induction of mitotic catastrophe leading to cell death. AgNPs downregulated the expression of several oncogenes associated with cancer cell proliferation and survival (cyclin D1, COX-2, HER-2, and miR622), but did not significantly reduce c-Myc expression. In conclusion, AgNPs derived from A. heterophyllus leaf extract have significant potential as a novel therapeutic agent in cancer treatment while preserving its biocompatibility, emphasizing the promise of sustainable and cost-effective synthesis of plant-based nanoparticles
Thymoquinone and madecassoside improve motor function in a rotenone-induced mouse model of early Parkinson’s disease: Role of dopamine, alpha-synuclein and mBDNF
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
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
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
Comparative efficacy of solifenacin and tamsulosin in alleviating stent-related symptoms: A systematic review and meta-analysis
Ureteral stents, commonly used in urology, can cause side effects affecting patient quality of life. However, studies on managing lower urinary tract symptoms showed inconsistencies due to the use of various alpha-blockers and antimuscarinic drugs. The aim of this study was to evaluate the effectiveness of combining tamsulosin and solifenacin therapy compared to tamsulosin and solifenacin monotherapy for treating stent-related symptoms. Randomized controlled trials assessing tamsulosin, solifenacin, or their combination for stent-related symptoms treatment were identified through a comprehensive search of four databases (PubMed, Scopus, Web of Science, and Cochrane) from January 2018 to December 2023. Ureteral stent symptom questionnaire (USSQ), international prostate symptom score (IPSS), visual analog scale (VAS), and quality of life (QoL) were pooled for meta-analysis. Eleven studies with a total of 1,627 patients were included in the quantitative analysis. Solifenacin significantly improved urinary symptoms (MD: 15.31; 95%CI: 0.36–30.26; p=0.040) and reduced the IPSS (MD: -2.52; 95%CI: -3.68–-1.36; p<0.00001) compared to the control group. Tamsulosin reduced urinary symptoms on the USSQ (MD: 14.27; 95%CI: 8.68–19.86; p<0.00001), general health problems (MD: 4.53; 95%CI: 2.13–6.94; p=0.0002), and IPSS (MD: -0.95; 95%CI: -1.86–-0.03; p<0.00001) compared to the control group. Solifenacin demonstrated a more significant reduction in the overall IPSS compared to tamsulosin (MD: -1.57; 95%CI: -2.85–-0.29; p=0.020). The combination of solifenacin and tamsulosin resulted in a significantly superior reduction in IPSS compared to solifenacin monotherapies (MD: -2.30; 95%CI: -3.23–-1.37; p<0.00001) and tamsulosin monotherapy (MD -3.17; 95%CI: -5.07–-1.27; p=0.00001). No significant differences were found between tamsulosin and solifenacin in terms of QoL (MD: 0.12; 95%CI: -0.01–0.26; p=0.070) and VAS (MD: 0.25; 95%CI: -0.95–1.44; p=0.690). In conclusion, solifenacin was more effective than tamsulosin in reducing stent-related symptoms, and the combination of tamsulosin and solifenacin was superior to either monotherapy in alleviating stent-related symptoms
Exploring factors contributing to falls in home-dwelling older adults: A cross-sectional study in Northeastern Thailand
Falls are the most common accidents among older adults in home settings. Older adults experience falls due to several risk factors. In 2005, Thailand became an aging society, with projections indicating that by 2021, older adults would represent the majority of the population, and by 2035, approximately 30 percent of the population would be older adults. Approximately 3 million fall episodes transpire among older adults each year in Thailand, leading to almost 60,000 hospitalizations. The aim of this study was to examine the factors associated with falls among older adults in northeastern Thailand, hypothesizing that characteristics such as cognitive capacity, visual acuity, hearing acuity, balance ability, and mobility are associated with fall risk in this population. A cross-sectional analytical study involved 264 older adults aged 60 years or older using a questionnaire and a battery of tests that assessed the participants’ cognitive capacity, eyesight proficiency, hearing ability, balancing ability, and mobility. The variables that exhibited a statistically significant association (p<0.05) were employed in a binary logistic regression analysis. The results revealed that falls among home-living older adults were significantly associated with sex, family size, congenital issues, and mobility. Older adults who were female and had a large family, congenital disorders, or mobility impairments were at a higher risk of falls, which emphasizes the need for personalized prevention strategies. It is recommended to adopt a proactive healthcare strategy to prevent falls and ensure safe living conditions. Interventions aimed at improving balance, mobility, and mental health, as well as encouraging an active lifestyle, may reduce the risk of falls among older adults living in the community. The findings may aid private and government agencies in developing effective fall prevention programs for older adults living at home
Probiotics-derived butyric acid may suppress systemic inflammation in a murine model of chronic obstructive pulmonary disease (COPD)
Systemic inflammation in chronic obstructive pulmonary disease (COPD) contributes to multimorbidity and a diminished quality of life. Probiotics, through the gut-lung axis, have shown potential to mitigate systemic inflammation; however, their specific role in COPD-related inflammation remains unclear. The aim of this study was to evaluate the efficacy of probiotics in reducing serum interleukin-6 (IL-6) levels by enhancing butyric acid production in a murine model of COPD. An in vivo experimental study with a post-test-only control group design was conducted using 30 C57BL/6 mice randomized into five groups: non-COPD healthy control, untreated COPD, COPD treated with bronchodilator, COPD treated with probiotics, and COPD treated with a combination of bronchodilator and probiotics. COPD was induced by six weeks of cigarette smoke exposure, followed by six weeks of treatment while continuing the smoke exposure. Caecal butyric acid and serum IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA) and gas chromatography, respectively. Caecal butyric acid levels were lowest in untreated COPD mice (1.2±0.28 mmol/L) and significantly increased with probiotic administration (6.6±4.43 mmol/L, p=0.010), exceeding levels observed in healthy controls (3.9±2.05 mmol/L). Serum IL-6 levels were highest in COPD-induced mice (19.4±6.71 pg/mL) and significantly reduced with administration of probiotics (13.5±0.43 pg/mL, p=0.035), approaching levels of healthy controls (13.0±2.24 pg/mL, p=0.847). A negative correlation was observed between butyric acid and serum IL-6 levels (r=-0.420; p=0.021), suggesting that higher butyric acid levels were associated with reduced systemic inflammation. These findings demonstrated that probiotics, via their metabolite butyric acid, effectively reduced systemic inflammation in a COPD mouse model, highlighting their potential as a therapeutic approach for managing COPD-related inflammation
Cardiomyopathy as the forgotten symptom of systemic lupus erythematosus in children: A case report
Cardiomyopathy is a rare clinical manifestation in pediatric systemic lupus erythematosus (SLE), with only a single case reported in the literature. Its identification in pediatric SLE is challenging due to its typically subclinical presentation and low incidence, which frequently result in delayed diagnosis and management. The aim of this study was to present a unique case of dilated cardiomyopathy, a rare cardiac complication of SLE, which can be life-threatening if not promptly recognized and treated. An 11-year-old boy was admitted to the emergency department of Murni Teguh Memorial Hospital, diagnosed with SLE based on the 2019 European Alliance of Associations for Rheumatology (EULAR) criteria, with a total score of 30 and a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of 16, indicating high disease activity. Clinical findings included oral ulcers, a non-pruritic hyperpigmented discoid macule, anemia, lymphopenia, positive both the direct and indirect Coombs tests, elevated D-dimer level, and pulmonary congestion. Initial treatment stabilized the patient condition, allowing transfer to the general ward by day five. Five days after admission, the patient developed palpitations and tachycardia, with a heart rate of 140 beats per minute. Electrocardiography showed sinus tachycardia, while echocardiography revealed all cardiac chambers dilation, left ventricular ejection fraction (LVEF) of 43%, moderate mitral regurgitation, and mild pulmonary regurgitation, subsequently diagnosed as dilated cardiomyopathy. Heart failure therapy was initiated with intravenous furosemide, oral ramipril, and digoxin. Palpitations and tachycardia resolved within two days. Following two weeks of treatment, the patient was discharged with stable vital signs. A one-month follow-up thoracic echocardiography demonstrated improved cardiomyopathy, with an LVEF of 53%. Cardiomyopathy in pediatric SLE is rare but can cause significant morbidity and mortality if undiagnosed. Its nonspecific presentation and immune-mediated pathogenesis make early detection challenging. Due to its rarity, it may be overlooked, highlighting the importance of comprehensive cardiac evaluation, including echocardiography, in children with suspected cardiac involvement
Exploring the potential of Laportea decumana extract compounds as COX-1 and COX-2 inhibitors: An in silico study
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
Preferences for a new vaccine against an emerging infectious disease: A discrete choice experiment among Millennials and Generation Z in Vietnam
The rising threat of emerging infectious diseases (EIDs) highlights the need to understand factors influencing vaccine adoption. The aim of this study was to explore the willingness to vaccinate and vaccine acceptance preferences among Millennials and Generation Z in Vietnam. Convenience sampling was conducted, after which a traditional discrete choice experiment was performed. Participants were tasked with selecting their preferred options from a set of eight vaccination choice tasks, each consisting of two alternatives distinguished by varying degrees of vaccine efficacy, side effects, influential endorsements, trusted sources, and disease susceptibility through literature reviews, expert interviews, and pilot tests. A minimum sample size of 375 participants was recruited via Internet-based and paper-based surveys. A latent class model was used to explore the heterogeneity in participant preferences, while a mixed logit model was employed to facilitate the computation of the predicted probabilities of vaccine acceptance. Among the 818 included participants, 494 (60.4%) were Millennials generation. The predicted probability of vaccine acceptance was 61.8%, with slight differences between Millennials (62.4%) and Generation Z (61.0%). Four latent classes with significant preference variations were identified. Class 1 (38%) was influenced by vaccine effectiveness, side effects, and health authority recommendations, showing lower opt-out rates. Class 2 (28%) prioritized vaccine effectiveness and authority recommendations but had higher opt-out rates and a stronger religious influence. Class 3 (23%) focused on vaccine effectiveness and side effects, with a tendency to opt-out. Class 4 (11%) valued high vaccine effectiveness and advice from family, with infection risks to family or local areas being significant motivators. Influential voices were more important in Classes 1 and 2, while side effects and effectiveness were prioritized in Classes 3 and 4. In conclusion, Vietnamese Millennials and Generation Z preferred vaccination when the vaccine had 90% efficacy, mild to moderate side effects, endorsements from the Ministry of Health, positive recommendations from family and social networks, and high exposure risks from family members
Projecting the impact of a national strategy to accelerate stunting prevention in East Nusa Tenggara, Indonesia, using the Lives Saved Tool
Stunting remains a critical public health issue in East Nusa Tenggara (ENT), Indonesia, with prevalence rates among the highest in the country, despite national efforts to reduce its occurrence. The aim of this study was to project the impact of the 2018–2024 National Strategy to Accelerate Stunting Prevention on children under five years old in ENT, using the Lives Saved Tool. A cross-sectional approach was employed, integrating data from various sources, including the 2020 Census of Indonesia, the Global Data Lab-Area Database, the Central Bureau of Statistics Republic Indonesia, the National Socioeconomic Survey, the 2017 Indonesia Demographic and Health Survey, the 2018 Basic Health Research, and the 2021 Indonesia Nutrition Status Survey. The analysis considered three scenarios: (1) a baseline scenario reflecting ENT’s 2017 coverage, maintained through 2028; (2) a scenario assuming Indonesia achieves the Health Plan Action Stunting targets; and (3) a projection of stunting rates based on ENT-specific coverage. Under scenarios 1 and 2, the prevalence of stunting was projected to decrease from 40.04% in 2018 to 39.82% and 39.78%, respectively, by 2028, with scenario 3 reflecting a similar trend. The findings revealed a sharp increase in the number of stunting cases averted among children under five years old between 2017 and 2021, followed by a more gradual decline, culminating in the 2028 projections: 2,249 children (scenario 2), 2,130 children (scenario 3), and 1,966 children (scenario 1). Breastfeeding promotion emerged as the most impactful intervention, accounting for over half of the total stunting cases averted under both Indonesia-wide and ENT-specific coverage scenarios. This was followed by interventions such as multiple micronutrient supplementation and vitamin A supplementation. The study highlights that reducing the prevalence of stunting among children requires a comprehensive prioritization of intervention strategies. The implementation of breastfeeding promotion, combined with appropriate complementary feeding practices, is expected to contribute significantly to achieving the sustainable development goal targets