Narra J (Journal)
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Metabolomic profiling and antimicrobial investigation of Aspergillus fumigatus LBKURCC269 and Bacillus paramycoides LBKURCC218 co-culture
Get PDFThe increasing resistance of pathogenic microbes to antibiotics is a major public health concern, necessitating the discovery of effective antimicrobial compounds. The aim of this study was to assess the bioactive metabolites produced by Aspergillus fumigatus LBKURCC269 and Bacillus paramycoides LBKURCC218 under three fermentation conditions: monoculture of each microorganism and their co-culture. Metabolite analyses initiated with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) followed with molecular networking–Global Natural Products Social Molecular Networking (GNPS) and molecular docking. Antimicrobial activity of the extracts was then conducted. Metabolite analysis using GC-MS identified key antimicrobial compounds, including 2,6-bis(1,1-dimethylethyl)-4-methylphenol, pentadecanoic acid, cyclopropane pentanoic acid, and 3-piperidinol. LC-HRMS, combined with multivariate analysis and GNPS molecular networking, revealed additional antimicrobial compounds, including novel pyrazine derivatives induced in co-culture fermentation. Molecular docking analysis of 3-(propan-2-yl)-octahydropyrrolo[1,2-a]pyrazine-1,4-dione demonstrated its potential as an antimicrobial agent by inhibiting topoisomerase IV and cytochrome monooxygenase with binding affinity of -5.34 kcal/mol and -5.6 kcal/mol, respectively. The antimicrobial assays showed that the co-culture fermentation extract had the strongest activity, with inhibition zones of 20.33±0.59 mm (Escherichia coli), 14.33±0.59 mm (Staphylococcus aureus), and 25.67±0.59 mm (Candida albicans). This study highlights the advantages of co-culture fermentation in enhancing the discovery of antimicrobial compounds. The findings underscore the potential of this approach to simplify chemical isolation and accelerate the identification of novel antimicrobial agents for pharmaceutical development
Comparative efficacy of solifenacin and tamsulosin in alleviating stent-related symptoms: A systematic review and meta-analysis
Get PDFUreteral 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
Therapeutic potential of thymoquinone in regulating p63, claudin, and periostin in chronic rhinosinusitis with nasal polyps: An animal model study
Get PDFHigh recurrence rate and the necessity for repeated surgical interventions contribute to the chronicity and treatment-resistant nature of chronic rhinosinusitis with nasal polyps (CRSwNP). Thymoquinone, known for its protective effects on epithelial integrity, has not been previously explored in CRSwNP. The aim of this study was to investigate the therapeutic potential of thymoquinone to restore epithelial integrity by assessing p63 transcription factor and claudin protein expressions, as well as periostin mRNA expression in an animal model. An in vivo study using post-test-only control group design was conducted in which male Wistar rats were randomly assigned to three groups, each consisting of 10 animals: healthy group, CRSwNP group, and thymoquinone-treated group for three weeks. Immunohistochemistry was used to analyze the p63 and claudin protein expressions, while periostin mRNA expression was quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). This study found that thymoquinone significantly reduced p63 transcription factor expression compared to the untreated CRSwNP group (p=0.009). Claudin protein expression was significantly higher in thymoquinone-treated group compared to CRSwNP group (p=0.007), indicating improved epithelial barrier function. Periostin mRNA expression showed no significant difference between healthy and thymoquinone-treated groups (p=0.564), but a significant decrease was observed in CRSwNP group compared to thymoquinone-treated group (p=0.000) and between the healthy and CRSwNP groups (p=0.002), suggesting attenuation of tissue remodeling and inflammation. In conclusion, thymoquinone could enhance sinonasal epithelial barrier integrity in CRSwNP by downregulating p63 transcription factor, upregulating claudin protein expression, and reducing periostin mRNA expression. These findings emphasize the potential of thymoquinone as a therapeutic agent to mitigate inflammation and tissue remodeling in CRSwNP, warranting further investigation as a novel treatment option
Plant-based synthesis of gold and silver nanoparticles using Artocarpus heterophyllus aqueous leaf extract and its anticancer activities
Get PDFGreen 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
Umbilical cord mesenchymal stem cell-derived secretome as a potential treatment for systemic lupus erythematosus: A double-blind randomized controlled trial
Get PDFUmbilical cord mesenchymal stem cell-derived (UCMSC-derived) secretome is anti-apoptotic, anti-inflammatory, antifibrotic, angiogenic, and tissue-regenerating. Thus, it may treat systemic lupus erythematosus (SLE). The aim of this study was to investigate the impact of the UCMSC-derived secretome on SLE patients' disease activity, using Mexican systemic lupus erythematosus disease activity index (MEX-SLEDAI) score, complement (C3 and C4) levels, tumor necrosis factor-alpha (TNF-α), anti-double-stranded DNA (anti-dsDNA), and interleukin-6 (IL-6) levels. This double-blind randomized controlled trial investigated the efficacy and safety of UCMSC-derived secretome in SLE patients with moderate disease activity. A total of 29 female patients were randomized into two groups to receive weekly 1.5 cc intramuscular injections of UCMSC-derived secretome or placebo (0.9% NaCl) for six weeks. Disease activity was assessed using the MEX-SLEDAI score, C3 and C4 levels, pro-inflammatory cytokines (IL-6 and TNF-α), and anti-dsDNA antibodies at baseline, Day 22, and Day 43. Results showed a significant reduction in MEX-SLEDAI scores in the secretome group compared to the placebo group (p<0.05). Complement C3 levels significantly increased in the secretome group on Day 43, indicating improved immune homeostasis, while C4 levels did not show significant differences between groups. IL-6 and TNF-α levels showed decreasing trends in the secretome group. Anti-dsDNA levels exhibited a decreasing trend in the secretome group, though not statistically significant. Importantly, no severe adverse events were observed, underscoring the safety of the intervention. UCMSC-derived secretome demonstrated immunomodulatory and anti-inflammatory effects, reducing disease activity in SLE patients. These findings suggest its potential as a safe and effective adjunct therapy for SLE, although further studies with larger sample sizes and extended follow-up periods are needed to validate these results
Redefining treatment paradigms: Early use of dapagliflozin and empagliflozin in acute heart failure – a systematic review and meta-analysis of randomized controlled trials
Get PDFSodium-glucose co-transporter 2 inhibitors (SGLT2i) have proven to significantly reduce mortality and rehospitalization in heart failure with reduced ejection fraction (HFrEF). Supported by the 2023 European Society of Cardiology (ESC) guidelines and the safety, tolerability, and efficacy of rapid optimization of heart failure (STRONG-HF) trial, SGLT2i offer improved outcomes with a favorable safety profile, emphasizing their pivotal role in HFrEF management. The aim of this study was to evaluate early initiation with dapagliflozin and empagliflozin, focusing on their efficacy and safety in acute heart failure (AHF). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched seven databases for randomized controlled trials on SGLT2i in AHF (2019–2024). Outcomes included all-cause mortality, heart failure (HF)-related events, all-cause rehospitalization, length of hospital stay, diuretic response, serum electrolytes, and adverse events (AEs). The Cochrane Risk of Bias 2 tool was used. Data were analyzed using a random-effects model and presented as standardized mean differences and risk ratios with 95% confidence intervals. A subgroup analysis was conducted based on intervention. Nine studies encompassing 1,417 patients with a generally low risk of bias were included. Initiating SGLT2i within five days of admission significantly reduced in-hospital all-cause mortality risk by 42% and in-hospital worsening HF during rehospitalization by 39%. SGLT2i also significantly reduced serious AEs risk by 27%. No significant differences were found in other outcomes, including specific AEs (acute kidney injury, hepatic injury, symptomatic hypotension, hypoglycemia, urinary tract infections, and diabetic ketoacidosis). The analysis showed homogeneity, with no significant differences between SGLT2i. The study highlights that initiating SGLT2i within five days of admission significantly reduces all-cause mortality and worsening HF during rehospitalization, with a better safety profile than placebo
Enhancing dermoscopic pigmented skin lesion classification: A refined approach using the pre-trained Inception-V3 architecture
Get PDFSkin cancer is one of the most prevalent cancers worldwide, with early diagnosis being critical for improving survival rates. Dermoscopy, a non-invasive imaging tool, is widely used for identifying pigmented skin lesions. However, its accuracy is heavily dependent on expert interpretation, which introduces variability and limits accessibility in resource-constrained settings. This highlighted the need for automated solutions to enhance diagnostic consistency and aid in early detection. The aim of this study was to develop a refined machine-learning framework for classifying pigmented skin lesions using dermoscopy images. We employed an enhanced Inception-V3 model, a state-of-the-art convolutional neural network, integrated with a simplified soft-attention mechanism, advanced data augmentation techniques, and Bayesian hyperparameter tuning. These innovations improved the model’s ability to accurately focus on and identify relevant lesion features, marking a significant advancement in the field. Using the ISIC-2019 dataset, a publicly available resource containing dermoscopy images classified into eight diagnostic categories, we implemented preprocessing steps such as resizing, cleaning, and data balancing. Additionally, ImageNet transfer learning and Bayesian optimization were applied to refine the model. The inclusion of a soft-attention mechanism further enhanced the model’s capacity to identify patterns within lesion images. Our model exhibited outstanding performance on the ISIC-2019 dataset, achieving a sensitivity of 98.5%, specificity of 99.62%, precision of 97.42%, accuracy of 97.38%, an F1 score of 97.34%, and an area under the curve (AUC) of 0.99. These metrics underscored the model’s superior capability in accurate and reliable classification of pigmented skin lesions, surpassing current benchmarks and demonstrating significant advancements over existing methodologies
Evaluating autologous peritoneum grafting for enhanced healing of bile duct injuries: A preliminary data from an animal study
Get PDFIncreased incidence of laparoscopic cholecystectomy-related bile duct injuries (BDIs), combined with its risk of serious complications and mortality, highlights the need for a more effective repair technique. Although the use of autologous graft in BDI repair has been promoted, the role of autologous parietal peritoneum remains underexplored. The aim of this study was to evaluate the effect of autologous parietal peritoneum grafts in rabbit models of partial BDI, emphasizing its effect on the expression of cluster of differentiation 68 (CD68) and transforming growth factor-β (TGF-β). An experimental post-test-only design was employed, using 27 male New Zealand rabbits (Oryctolagus cuniculus) aged 8–10 months. The rabbits were allocated into three groups: control (primary closure), autologous parietal peritoneum graft, and autologous gallbladder graft. Partial BDI measuring 15×5 mm were surgically created and repaired according to group assignments. The expression of CD68 and TGF-β were measured via enzyme-linked immunosorbent assay (ELISA), while the anastomosis was pathologically examined through hematoxylin and eosin (H&E) staining on days 3, 7, and 14 post-surgery. Statistical analysis was performed using analysis of variance (ANOVA) followed by Bonferroni post hoc tests. No statistically significant difference was observed in the expression of CD68 or TGF-β among the three treatment groups on days 3, 7, and 14 post-surgery, indicating that the effects of autologous parietal peritoneum graft were comparable to the control and the autologous gallbladder graft in promoting wound healing. Fibroblast density on day 3 was significantly lower in the parietal peritoneum group (p=0.040), reflecting delayed recruitment, but normalized by day 14, indicating successful integration and remodeling. The study highlights the potential role of autologous parietal peritoneum grafts for BDI
Effects of porang glucomannan combined with a high-protein diet on oxidative stress, inflammation, and aging markers in D-galactose-induced rats
Get PDFAging is a predominant risk factor for several diseases associated with reduced life expectancy. To address this risk factor, several studies have proposed the combined use of porang glucomannan and a high-protein diet to improve various aging markers. The aim of this study was to determine the effects of porang glucomannan and high-protein combination diet as an anti-aging agent. An experimental study using a post-test-only control group design was conducted using Sprague Dawley white rats. The animals were randomly divided into four groups with different treatments as follows: normal control, D-galactose, high-protein diet, and a combination of porang glucomannan and high-protein combination diet. Blood samples were then collected from the ophthalmic vein on day 58 for biomarker measurement using the enzyme-linked immunosorbent assay (ELISA) method. The parameters measured were superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), insulin growth factor-1 (IGF-1), NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), growth differentiation factor-11 (GDF11), and α-Klotho levels. The results showed that the combination of porang glucomannan and high-protein diet could improve oxidative stress, inflammation, and aging markers. The analysis of variance (ANOVA) test followed by post-hoc least significant difference (LSD) showed significant differences between the combination diet and high protein group (p<0.0001). In addition, the average levels of oxidative stress markers (SOD and MDA) in porang glucomannan and high-protein combination group were improved significantly. Similar results were also obtained for inflammatory markers (IL-6 and TNF-α) and aging markers (NLRP3, IGF-1, GDF-11, and α-Klotho). The mean NRLP-3 levels in glucomannan and high-protein combination group were not significantly different compared to control. The study highlights that the combination of porang glucomannan and a high-protein diet effectively improved various aging markers
Improving pelvic floor muscle strength in women with postpartum stress urinary incontinence using electromagnetic stimulation therapy: A randomized controlled trial
Get PDFElectromagnetic stimulation (EMS) has emerged as a potential alternative for managing urinary incontinence in women. However, research directly comparing EMS to Kegel exercises in cases of postpartum stress urinary incontinence (SUI) is limited. The aim of this study was to assess the effectiveness of EMS (improvement of the symptoms, incontinence severity and pelvic floor muscle strength) and patient compliance with the therapy in postpartum women with SUI. A single-blind randomized clinical trial was conducted involving postpartum women diagnosed with SUI at least three months after delivery. The EMS group received the therapy three times a week for five weeks, while the Kegel group was instructed to perform daily exercises for eight weeks. Improvement of the symptoms and incontinence severity were evaluated using the Urogenital Distress Inventory-6 (UDI-6) and a 1-hour pad test, respectively, while pelvic floor muscle strength was measured with a perineometer. Both groups showed significant improvements in UDI-6 scores, 1-hour pad test results and pelvic floor muscle strength compared to before treatment. However, the EMS group had significantly greater muscle strength than the Kegel group (16.5 vs 8.0 cmH2O, p=0.006). The UDI-6 scores, 1-hour pad test results and patients’ compliance were not significantly different between EMS and Kegel groups. EMS demonstrated a greater ability to enhance pelvic floor muscle strength than Kegel exercises. These findings suggest that EMS may be a more effective option for enhancing pelvic floor muscle strength in postpartum women