Narra J (Journal)
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Fungistatic activity and mechanism of Caulerpa racemosa, Caulerpa lentillifera fractions and caulerpin metabolite against pathogenic fungi
The increasing prevalence of azole resistance in various fungal species presents a significant concern, highlighting the urgent need for new antifungal agents. The aim of this study was to investigate the antifungal activity of fractions from Caulerpa racemosa, C. lentillifera, and caulerpin against three species: Aspergillus flavus, A. niger, and Candida albicans. The Caulerpa extracts were obtained through maceration with 96% ethanol, followed by fractionation using vacuum liquid chromatography. Antifungal activity was assessed using the broth microdilution method, while fungal growth kinetics were evaluated through time-kill curves. Bioautography was employed to identify inhibitory compounds, while liquid chromatography high-resolution mass spectrometry (LC-HRMS) was utilized to detect the contents of the extracts and fractions. Scanning electron microscopy (SEM) was used to observe the fungal structure, and the absorbance at 260/280 nm was measured to evaluate the cell leakage. LC-HRMS identified numerous compounds in C. racemosa and C. lentillifera with antifungal activities, including fatty acids, terpenes, alkaloids, flavonoids, and coumarins. The results indicate that the fractions of both Caulerpa did not inhibit the growth of A. flavus and A. niger, but effectively inhibited C. albicans. Among the fractions, F3CR and F4CL exhibited the highest antifungal efficacy against C. albicans, with minimum inhibitory concentrations (MICs) ranging from 64 to 128 µg/mL. Caulerpin, the primary metabolite of Caulerpa, also demonstrated significant inhibition, with an MIC of 256 µg/mL. The findings suggested that F3CR, F4CL, and caulerpin possessed fungistatic properties. Bioautography results revealed clear zones in the colonies, indicating inhibited fungal growth. The SEM observations showed that fungal cells became rough, perforated, and damaged, which was confirmed by the increase in absorbance at 260/280 nm, suggesting the release of cellular components such as nucleotides and proteins. In conclusion, both Caulerpa species and caulerpin are promising candidates for developing new antifungal agents against C. albicans
Primary malignant giant cell tumor (PMGCT): Diagnosis and management challenges in low resource settings
Bone primary malignant giant cell tumor (PMGCT) cases are extremely rare, and the optimal management remains unclear. This case report details the diagnosis and successful management of PMGCT in a 45-year-old female presenting with left knee pain, swelling, and restricted movement for one year. Accompanying weight loss and loss of appetite led the patient to seek tertiary care after unsuccessful prior treatment. Imaging, including X-ray and magnetic resonance imaging (MRI), revealed a tumor measuring 7.9 × 7.7 × 6.6 cm, and histopathological examination using fine needle aspiration cytology confirmed the diagnosis of PMGCT. A multidisciplinary approach was taken, involving orthopedic surgery to remove the tumor successfully, and physiotherapy for post-operative care. The patient underwent tumor excision and curettage under spinal and epidural anesthesia, followed by a week of bed rest, and then physiotherapy was started to aid in limb mobilization. Post-operative care involved blood transfusions, femoral artery stenting, continued physiotherapy and adjuvant radiotherapy, initiated two weeks post-surgery, with a total dose of 50 Gy delivered in 25 sessions to reduce the risk of recurrence. Initial monthly follow-ups, later transitioning to quarterly, showed improved joint mobility and function, with no recurrence at the 9-month follow-up. This case highlights the importance of early diagnosis and a multidisciplinary approach in managing PMGCT. Collaboration across specialties contributed to the positive outcome, even in a resource-limited setting. Long-term monitoring remains essential to detect recurrence, and further research is needed to refine treatment strategies for malignant GCTs
Exploring the role of polysaccharides in mitigating organ damage caused by pesticide-induced toxicity: A systematic review and meta-analysis of in vivo studies
Although polysaccharides have demonstrated potential in alleviating dysbiosis, the overall impact of polysaccharides on minimizing oxidative stress and organ damage in vivo has not been thoroughly investigated. The aim of this study was to investigate the comprehensive effects of polysaccharides in mitigating pesticide toxicity in animal studies, focusing on biomarkers related to oxidative stress, antioxidant activity, kidney injury, lipid profiles, liver function, and the preservation of liver and kidney weights. A systematic search was conducted across nine indexed databases, including PubMed, Cochrane CENTRAL, Taylor & Francis, Scopus, Sage, EBSCO, ProQuest, ScienceDirect, and Google Scholar. Rayyan.ai was used to screen in vivo studies that met the predefined inclusion and exclusion criteria. The quality of the selected in vivo studies was evaluated using SYRCLE’s Risk of Bias tool, specifically designed for animal studies. Thirteen randomized animal studies, comprising 330 mice and rats, were included in the analysis. The findings revealed that polysaccharides significantly increased antioxidant levels, including catalase (CAT) (p<0.00001), superoxide dismutase (SOD) (p<0.00001), glutathione peroxidase (GPx) (p<0.00001), and reduced glutathione (GSH) (p<0.00001). Polysaccharides also significantly reduced oxidative stress markers, such as malondialdehyde (MDA) (p<0.00001) and nitric oxide (NO) (p<0.0001), as well as kidney injury biomarkers, including serum creatinine (p<0.00001) and urea (p<0.00001). Additionally, improvements in lipid profiles were observed, with significant reductions in triglycerides (TG) (p=0.04) and total cholesterol (TC) (p<0.00001). However, there were no significant differences in high-density lipoprotein (HDL) (p=0.28) and low-density lipoprotein (LDL) (p=0.32) levels. Polysaccharides significantly alleviate liver biomarkers, including aspartate transaminase (AST) (p<0.0001), alanine transaminase (ALT) (p<0.005), and alkaline phosphatase (ALP) (p<0.0001). Polysaccharides also contributed to the maintenance of liver weight (p=0.009), although no significant differences were observed in kidney weights (p=0.81). The study highlights that polysaccharides exert significant effects in enhancing antioxidant levels, reducing oxidative stress and organ damage biomarkers, and preserving liver weights
Effect of clove flower extract (Syzygium aromaticum) administration timing on skeletal muscle damage induced by eccentric exercise: An in vivo study
Eccentric exercise often leads to oxidative stress, inflammation, and muscle damage that impair athletic performance. To counter these adverse effects, clove flower extract (Syzygium aromaticum) offers promising potential as a natural remedy to promote muscle repair with its potent antioxidant and anti-inflammatory properties. The aim of this study was to assess the effects of clove flower extract administration timing on oxidative stress and inflammatory responses in skeletal muscle damage induced by acute eccentric exercise in mice. This study used a post-test-only control group design, involving 35 male mice (Mus musculus, Balb/c) randomly divided into five groups: a healthy control group (HC) with no exercise and no treatment, a negative control group (NC) with exercise but no treatment, and three treatment groups: T1, T2, and T3 (clove flower extract 24 hours before exercise, immediately after exercise, and 24 hours after exercise, respectively). The treatment groups received a single dose of clove flower extract (500 mg/kg body weight). The skeletal muscle damage of mice was collected for the NADPH oxidase (NOX) and superoxide dismutase (SOD) activities using spectrophotometry, and toll-like receptor 4 (TLR4) and interleukin-8 (IL-8) measurements using enzyme-linked immunosorbent assay (ELISA). Moreover, the skeletal muscle damage was analyzed through the histopathological method. Data were analyzed using one-way analysis of variance (ANOVA) followed by Fisher's least significant difference (LSD) tests as a post hoc test. The result showed that clove flower extract significantly reduced NOX activity (p=0.049) and IL-8 levels (p=0.032), and increased SOD activity (p=0.001) while not significantly affecting the TLR4 levels (p=0.532). Moreover, the results showed a significant reduction in muscle damage (p=0.001). The study highlights that the administration of clove flower extract (500mg/kg bw) can be given 24 hours before, immediately after exercise, or 24 hours after exercise to prevent muscle damage
Comprehensive investigation of Litsea cubeba antibacterial and antifungal activities across solid, liquid, and vapor phases against key human pathogens
The escalating global incidence of antimicrobial resistance poses a significant public health challenge. In response, exploring alternative antimicrobial agents, particularly derived from plants, becomes crucial to alleviate the selective pressure exerted by conventional antibiotics. The aim of this study was to characterize the composition of essential oil extracted from Litsea cubeba fruits and to evaluate its antimicrobial potential, along with its major compound, across solid, liquid, and vapor phases. The antimicrobial activity was assessed against a diverse range of human pathogenic Gram-positive bacteria (n=8), Gram-negative bacteria (n=34), filamentous fungi (n=2), and yeast (n=1). Disk diffusion, broth macrodilution, and vapor-phase diffusion methods were employed. This study found that all phases of L. cubeba essential oil and purified limonene exhibited broad-spectrum bactericidal and fungicidal activities (solid-phase: inhibition zone diameter (IZD) 19 mm vs 14 mm; liquid-phase: minimum inhibitory concentration (MIC) 2.0 mg/mL vs 4.0 mg/mL; vapor-phase: IZD 90 mm vs 45 mm), with superior efficacy against filamentous fungi and yeast compared to bacteria (solid-phase: IZD 90 mm vs 17.5 mm; liquid-phase: MIC 2.0 mg/mL vs 0.06 mg/mL; vapor-phase: IZD 90 mm vs 12.5 mm; all p-values<0.05). Among bacteria, solid-phase L. cubeba essential oil demonstrated increased activity against Staphylococcus saprophyticus and Acinetobacter lwoffii whereas liquid-phase L. cubeba essential oil had optimal activity against Streptococcus agalactiae and Elizabethkingia meningoceptica. Notably, Trichophyton rubrum, Nannizzia gypsea, and Candida albicans displayed high susceptibility to all phases of L. cubeba essential oil. These findings highlight the potential activity of L. cubeba essential oil, across its various phases, as a promising alternative antimicrobial agent against medically significant pathogens, providing essential baseline information for further exploration and development of L. cubeba essential oil in the pursuit of combating antimicrobial resistance
Divergent roles of circulating miR-133 and miR-155 in modulating angiotensin II levels among hypertensive patients in Melanesian and non-Melanesian populations
The therapeutic approach to hypertension often varies across racial and ethnic groups; however, antihypertensive treatments have not yet been tailored to account for these variations in Indonesia, a country with diverse racial and ethnic groups. In addition, microRNA-133 (miR-133) and microRNA-155 (miR-155) play critical roles in cardiac muscle homeostasis and inflammatory responses, but their specific functions in hypertension remain unclear. The aim of this study was to investigate the correlation between circulating miR-133 and miR-155 levels and angiotensin II (ANG-II) levels in hypertensive patients from Melanesian and non-Melanesian populations in Indonesia. A cross-sectional study was conducted in Jayapura, Indonesia among Melanesian and non-Melanesian hypertensive patients. The levels of ANG-II were quantified using sandwich ELISA, while the relative expression of miR-133 and miR-155 levels were measured by real-time PCR. Differences between the two groups were assessed using the Mann-Whitney test, and correlations between miR and ANG-II levels were determined using the Spearman correlation test. The relative expression levels of miR-133 and miR-155 in the Melanesian group were significantly higher than in the non-Melanesian group; 6.94-fold (3.85 vs 0.55) and 2.1-fold higher (0.19 vs 0.09), respectively. MiR-133 had a moderate negative correlation with ANG-II in both Melanesian (r=-0.538; p<0.001) and non-Melanesian (r=-0.649; p<0.001). However, miR-155 had no significant correlation with ANG-II levels in either the Melanesian group (p=0.551) or non-Melanesian group (p=0.159). This study highlights that miR-133 levels are significantly correlated with ANG-II concentrations in both Melanesian and non-Melanesian hypertensive patients, suggesting that miR-133 may play a regulatory role in the ANG-II pathway. These findings provide insights into the potential of miR-133 as a biomarker for hypertension management in diverse populations
Mechanistic insights into the anticancer, anti-inflammatory, and antioxidant effects of yellowfin tuna collagen peptides using network pharmacology
Marine-derived collagen peptides have been acknowledged for their therapeutic potential, especially in cancer therapy and inflammation management. The aim of this study was to investigate the molecular mechanisms that contribute to the anticancer, anti-inflammatory and antioxidant properties of yellowfin tuna collagen peptides (YFTCP) utilizing a network pharmacology approach. The YFTCP was extracted from the bones of yellowfin tuna (Thunnus albacares) and subsequently hydrolyzed with trypsin. Seventeen peptides were discovered using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS). A network pharmacology method was utilized to investigate the interactions between the discovered peptides and their biological targets. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify pertinent biological pathways involved in the anticancer, antioxidant, and anti-inflammatory effects of these peptides. GO analysis revealed key associations between YFTCP and critical cancer- and inflammation-related genes encoding proteins such as CCND1, SRC, AKT1, IL-1β, TNF, and PPARG, which exhibited significant interactions. These proteins are essential for the regulation of the cell cycle, the development of tumors, and the response to inflammatory stimuli. The KEGG analysis also revealed that YFTCP was involved in a number of critical pathways, such as endocrine resistance, cancer pathways, Kaposi sarcoma-associated herpesvirus infection, proteoglycans in cancer, and human cytomegalovirus infection. These findings highlight the potential use of YFTCP as a multifaceted therapeutic agent, indicating their role in regulating important biological pathways associated with cancer development and inflammation. This study provides new valuable insights into the pharmacological properties of YFTCP, paving the way for future studies and drug development focused on these bioactive peptides
CTLA-4 +6230G>A polymorphism and its impact on CTLA-4 level and risk of hepatocellular carcinoma: A case-control study in Batak patients with chronic hepatitis B
Genetic polymorphisms in cytotoxic T-lymphocyte-associated protein 4 gene (CTLA-4) vary by ethnic background, necessitating population-specific studies. The aim of this study was to assess the association between the CTLA-4 +6230G>A polymorphism, serum CTLA-4 level, and hepatocellular carcinoma (HCC) in Batak patients with chronic hepatitis B, a group with high hepatitis B virus (HBV) endemicity. A case-control study was conducted among cases (Batak patients with chronic hepatitis B and HCC) and controls (chronic hepatitis B without HCC). Genotyping of the CTLA-4 +6230G>A polymorphism was performed using the TaqMan SNP Genotyping Assay. Serum CTLA-4 level was quantified using enzyme-linked immunosorbent assay (ELISA). Patient’s demographic, clinical and laboratory data were recorded and assessed including age, sex, body mass index (BMI), smoking history, cirrhosis status, HBV DNA level, liver function markers (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), hepatitis B e-antigen (HBeAg) status, smoking history, and alcohol consumption. This study found that G allele was significantly associated with an increased risk of HCC (OR: 2.69; 95%CI: 1.21–6.00; p=0.013). Individuals with GG/AG genotypes had a 2.89-fold higher risk of developing HCC compared to those with the AA genotype (p=0.032). Serum CTLA-4 level was significantly elevated in G allele carriers (GG: 159.9±57.1 pg/mL vs AA: 83.7±44.7 pg/mL; p<0.001). Multivariate analysis identified cirrhosis as the strongest predictor of HCC (OR: 7.60; p<0.001), followed by elevated ALT (OR: 3.42; p=0.018) and high HBV DNA levels (OR: 2.31; p=0.024). In conclusion, the CTLA-4 +6230G>A GG/AG genotype and elevated serum CTLA-4 level were significantly associated with an increased risk of HCC in Batak individuals with chronic HBV infection. Further research is needed to explore additional CTLA-4 polymorphisms and immune regulatory mechanisms in HBV-related HCC to improve risk stratification and therapeutic strategies
Ivermectin and dexamethasone combination induces apoptosis in SUP-B15 cell line
The development of glucocorticoid resistance has complicated the management of acute lymphoblastic leukemia (ALL), leading to increased mortality rates. Ivermectin, a low-cost and well-established anthelmintic, exhibits anticancer potential and may enhance glucocorticoid toxicity in ALL, offering a possible strategy to overcome resistance. The aim of this study was to evaluate the apoptotic effect of combining ivermectin with dexamethasone in ALL. ALL SUP-B15 cells were cultured under standard conditions before treatment with dexamethasone (200 nM) alone or combined with ivermectin (5, 10, and 20 µM), with an untreated group serving as the control. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay by measuring cell viability and inhibition. Apoptosis was evaluated through BAX, BCL-2, and CASP3 gene expression analysis using reverse transcription-polymerase chain reaction (RT-PCR). The findings revealed that the combination of ivermectin and dexamethasone was superior in the repression of ALL cell viability compared to control (p<0.001). The combination of dexamethasone 200 nM + ivermectin 20 μM demonstrated the most significant cell inhibition of 38.16±0.04% (p<0.001) and produced the lowest cell viability of 61.84±0.05% (p<0.001). Moreover, the combination of dexamethasone 200 nM + ivermectin 20 μM demonstrated superior upregulations of BAX (p<0.001) and CASP3 (p<0.001). In conclusion, the addition of ivermectin (5 µM) to dexamethasone regimen (200 nM) increases its cytotoxic and apoptotic activities against SUP-B15 cell line as observed by the CASP3 and BAX upregulation. Studies to confirm the enhanced anticancer activity by this combination by observing the protein levels and animal studies are warranted
Improved sanitation and co-occurrence of anemia and stunting in Indonesian children: A retrospective cohort study
Anemia and stunting are major public health concerns in low- and middle-income countries, including Indonesia, with significant impacts on child development, morbidity, and mortality. The aim of this study was to assess the effect of improved sanitation on the co-occurrence of anemia and stunting (CAS) in Indonesian children using pooled data from the Indonesian Family Life Survey (IFLS) across three waves, from IFLS 3 in 2000, IFLS 4 in 2007, and IFLS 5 in 2014. The sample included 839 children aged 1–5 years with complete anthropometric and hemoglobin data, measured in 2000 as the baseline cohort and followed across subsequent waves. The main independent variable was improved sanitation, and other covariates included maternal and child characteristics, parental factors, and socio-economic status. Multinomial logistic regression was used to assess the impact of sanitation over time. The prevalence of CAS was 30.75% in 2000, 6.08% in 2007, and 4.29% in 2014. Stunting-only prevalence increased from 16.21% in 2000 to 27.41% in 2007 but decreased to 19.31% in 2014. Anemia-only prevalence decreased from 31.23% in 2000 to 10.25% in 2007 and slightly rose to 16.92% in 2014. The analysis found that children with unimproved sanitation were at significantly higher risk of CAS (crude relative risk ratio (RRR): 2.49; 95% confidence interval (CI): 1.92–3.23), which decreased after adjusting for confounding factors (adjusted RRR: 1.55; 95%CI: 1.12–2.14). Similarly, the risk for anemia was higher in children with unimproved sanitation (adjusted RRR: 1.43; 95%CI: 1.07–1.90). However, the risk for stunting was not statistically significant after adjustment. This study underscores the importance of improved sanitation in reducing anemia and stunting but also highlights the need to address other factors, such as nutrition, maternal health, and socioeconomic inequalities, through comprehensive public health policies