BACKGROUND: Synthetic food preservatives are widely used to improve food stability and shelf life, but prolonged exposure may contribute to oral and gastrointestinal carcinogenesis. Epidermal growth factor receptor (EGFR)–phosphoinositide 3-kinase (PI3K)–protein kinase B (Akt)–mammalian target of rapamycin (mTOR) axis plays a pivotal role in regulating tumor initiation and progression; however, the potential interactions with cancer-related signaling proteins remain poorly understood. This study computationally evaluated the predicted binding interactions of commonly used synthetic food preservatives with proteins using molecular docking. METHODS: Propyl gallate (PG), butylated hydroxyanisole (BHA), tertiary-butylhydroquinone (TBHQ), potassium sorbate (PS), sodium benzoate (SB), and sodium metabisulfite (SMB) were evaluated for physicochemical properties using SwissADME. Molecular docking with EGFR, PI3K, Akt-1, and mTOR was performed using CB-Dock 2.0. Predicted ligand–protein interactions were analyzed using BIOVIA Discovery Studio 2016 and root mean square fluctuation (RMSF) was evaluated using CABS-flex 3.0. RESULTS: PG and BHA exhibited the most predicted binding affinities among the investigated preservatives. PG showed the strongest interactions with EGFR (−6.1 kcal/mol), PI3K (−6.8 kcal/mol), and mTOR (−6.7 kcal/mol), whereas BHA demonstrated the highest affinity toward PI3K (−6.8 kcal/mol) and Akt-1 (−6.5 kcal/mol). These interactions were supported by multiple hydrogen bonds, hydrophobic interactions, and van der Waals contacts. CONCLUSION: PG and BHA exhibited the highest binding affinity toward proteins of the EGFR–PI3K–Akt–mTOR associated with oral and gastrointestinal carcinogenesis. These computational findings provide a basis for future experimental studies to determine the biological relevance of the predicted protein–ligand interactions under long-term dietary exposure. KEYWORDS: synthetic food preservatives, molecular docking, oral carcinogenesis, gastrointestinal carcinogenesis
BACKGROUND: Current management of traumatic brain injury (TBI) is primarily directed toward preventing secondary brain injury, while specific pharmacological therapies targeting post-traumatic neuroinflammation remain limited. Bioactive constituents of Nigella sativa, particularly thymoquinone, have demonstrated anti-inflammatory and antioxidant properties that may modulate mechanisms involved in secondary brain injury. This study was conducted to evaluate the effects of oral N. sativa oil on serum interleukin (IL)-1β and IL-10 levels as inflammatory parameters, neurological function and necrosis in a rat model of TBI. METHODS: Sixteen male Wistar rats underwent Marmarou weight-drop TBI and were randomly assigned into two groups given either oral N. sativa oil or distilled water (n=8/group) for 7 days. Serum IL-1β and IL-10 concentrations were measured using rat-specific enzyme-linked immunosorbent assays (ELISA), and neurological function was assessed using the modified Neurological Severity Score (mNSS) at post-injury baseline and on treatment day-1, -3, and -7. After day-7, brain tissue was examined using hematoxylin–eosin (H&E) staining, and necrotic-cell count was assessed. RESULTS: IL-1β concentrations were significantly lower in the N. sativa group from day-1 onward, whereas IL-10 concentrations were significantly higher and mNSS scores were significantly lower from day-3 onward. By day-3, all three outcomes differed significantly: lower IL-1β (56.38±10.21 vs. 111.98±47.64 pg/mL; p=0.013), higher IL-10 (102.38±33.42 vs. 40.20±6.02 pg/mL; p=0.001), and lower mNSS (median: 4 (3-5) vs. 5 (5-6); p=0.003) than placebo group. These differences persisted through day-7, which also supported by lower necrotic-cell counts in the N. sativa group (3164.13±771.38 vs. 4028.38±204.58; p=0.008). CONCLUSION: Administration of oral N. sativa oil shifted the circulating cytokine profile toward an anti-inflammatory pattern and was accompanied by better neurological function and fewer neuronal necrosis after TBI. These findings suggest that N. sativa oil may have beneficial effect on neuroinflammation after TBI. KEYWORDS: Nigella sativa, traumatic brain injury, interleukin-1 beta, interleukin-10, neuroinflammation, modified Neurological Severity Score
BACKGROUND: Chronic inflammation contributes to diabetes-associated fibrosis, through persistent hyperglycemia, leading to increased interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and collagen levels. While metformin effectively controls blood glucose, it may not adequately suppress these pathogenic pathways. Asiatic acid has demonstrated anti-inflammatory and antifibrotic properties, although its effects within a direct-contact macrophage–fibroblast microenvironment such as in co-culture models remain unclear. This study was conducted to evaluate the effects of asiatic acid on Il6, Tgfb1, and soluble collagen levels in a RAW 264.7–NIH 3T3 co-culture under high-glucose and lipopolysaccharide (HG–LPS) stimulation. METHODS: RAW 264.7 and NIH 3T3 cells were co-cultured at ratios of 1:1–1:6, and the selected co-culture was treated with asiatic acid (2.5, 5.0, and 10.0 µg/mL) for 24 h while HG–LPS stimulation was maintained. Unstimulated NIH 3T3 monocultures and untreated HG–LPS co-cultures served as controls. The inflammatory and profibrotic markers such as Il6 and Tgfb1 mRNA expression were quantified by polymerase chain reaction (PCR), and soluble collagen was measured using a modified Sirius Red assay. RESULTS: Among the tested ratios, the 1:1 co-culture exhibited the highest Tgfb1 mRNA expression (0.35±0.02) and soluble collagen level (1.30±0.00) and was selected for subsequent experiments, whereas Il6 mRNA expression did not differ significantly among co-culture ratios. Under HG–LPS stimulation, Il6 and Tgfb1 mRNA expression increased 3.5-fold and 10.3-fold, respectively, compared with unstimulated NIH 3T3 monocultures. Asiatic acid significantly reduced Il6 mRNA expression at 5.0 and 10.0 µg/mL, Tgfb1 mRNA expression at 2.5 µg/mL, and soluble collagen levels at all tested concentrations, indicating a non-monotonic concentration–response pattern. CONCLUSION: The 1:1 RAW 264.7–NIH 3T3 co-culture was the most responsive under HG–LPS stimulation and could be in vitro platform for investigating macrophage–fibroblast interactions under hyperglycemic inflammatory conditions. Asiatic acid modulated Il6 and Tgfb1 mRNA expression and soluble collagen levels in RAW 264.7–NIH 3T3 co-culture, which suggest that Asiatic acid may be potential for the management of fibrotic inflammation. KEYWORDS: co-culture, collagen, fibroblast dysfunction, NIH 3T3 fibroblast, RAW 264.7 macrophage
BACKGROUND: Cyclea barbata Miers has been identified as a phytoestrogenic candidate with comparable estrogen receptors (ER)α binding activity with 17β estradiol. Though phytoestrogens are reported to modulate reproductive and hormonal physiology, but no systematic in vivo toxicological evaluation of C. barbata extract has been reported. Therefore, this study was conducted to evaluate the acute and subacute oral toxicity of the ethanol extract of C. barbata (EECB) in Wistar rats. METHODS: For acute toxicity, rats received single oral doses of 2,000 or 5,000 mg/kg BW and were observed for 14 days. For subacute toxicity, EECB was administered orally at doses of 100–500 mg/kg BW/day for 28 consecutive days. Body weight, relative organ weights, haematological and biochemical parameters, and histopathological changes in major organs were evaluated. RESULTS: No mortality occurred at 2,000 mg/kg BW in either sex, whereas mortality was observed only in female rats at 5,000 mg/kg BW (20%). EECB was therefore classified as GHS Category 5 or unclassified (LD50 >2,000 mg/kg BW), indicating low acute oral toxicity. Repeated administration for 28 days caused no significant changes in body weight, organ weights, serum biochemical markers, or histopathological findings. However, a significant reduction in white blood cell counts was observed at doses ≥400 mg/kg BW/day (p<0.05). The subacute no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect-level (LOAEL) were established at 300 and 400 mg/kg BW/day, respectively. CONCLUSION: Based on the parameters assessed, the acute NOAEL for EECB was 2,000 mg/kg BW, while the subacute NOAEL and LOAEL for EECB were 300 and 400 mg/kg BW/day, respectively. These findings indicate that EECB might be safe at moderate doses, providing in vivo evidence supporting its further development as a phytoestrogenic agent. KEYWORDS: Cyclea barbata Miers, ethanol extract, acute toxicity, subacute toxicity, haematological parameters
BACKGROUND: Diabetes mellitus often exacerbated by cigarette smoke, which disrupts glucose homeostasis and lipid metabolism. Mango (Mangifera indica L.) and lime (Citrus amblycarpa) peels contain various phytochemical compounds, including those are reported to have metabolic and cytoprotective properties, but their combined nanoparticle formulation in cigarette smoke-exposed diabetes cases remains unexplored. Therefore, this study was conducted to evaluate the synergistic effect of mango-lime peel nanoparticles (NanoMC) on glycemic control, lipid profiles, and pancreatic cell damage in cigarette smoke-exposed diabetic rats. METHODS: Mango and lime peel ethanol extract was prepared into nanoparticles using emulsion-solvent evaporation method and followed by sonication and homogenization, and subsequently divided into three concentration groups. Rats were diabetic-induced and smoke-exposed, before being treated with/without Simvastatin + Glibenclamide, 20, 40, or 80 mg/kgBW NanoMC. Parameters including blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-β), hemoglobin A1c (HbA1c), and lipid profiles were then measured. To evaluate pancreatic cell damage, the pancreatic tissue was collected, fixed, and then evaluated by using Hematoxylin and Eosin (H&E) staining. RESULTS: NanoMC administration significantly reduced blood glucose, HbA1c, triglycerides, cholesterol, and low-density lipoprotein (LDL) levels (p<0.05). NanoMC treatment also increased insulin levels, HOMA-β, and high-density lipoprotein (HDL). After the treatment with NanoMC, particularly with 80 mg/kgBW concentration, fewer degenerative and necrotic cells were found compared to the other groups, showing its ability to attenuate pancreatic cell damage. CONCLUSION: The combination of NanoMC could improve glycemic status, modulate lipid profiles, and improved pancreatic cell damage in diabetic rats exposed to cigarette smoke. KEYWORDS: Mangifera indica, Citrus amblycarpa, nanoparticles, diabetes mellitus, cigarette smoke, lipid profiles, pancreatic histopathology
BACKGROUND: Prostate-specific antigen (PSA) is frequently used for prostate cancer screening and diagnosis, however its low specificity and incapacity to differentiate aggressive from indolent disease reduces its clinical utility. It is necessary to identify biomarkers that can complement PSA to increase the prognostic accuracy of prostate cancer. Emerging evidence suggests that androgen-related factors and immune mediators are involved in prostate cancer progression. Therefore, to identify more accurate markers of prostate cancer progression, several androgen-related and immunological parameters were evaluated alongside serum PSA to determine their potential as complementary prognostic biomarkers. METHODS: A cross-sectional study was performed involving 60 prostate cancer subjects age ranged 50-74 years and 60 healthy men within the same age range as control. Blood samples from subjects and controls were collected, then testosterone, dihydrotestosterone (DHT), androgen receptor (AR), prostatic acid phosphatase (PAP), interleukin (IL)-8, cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), transforming growth factor-β (TGF-β), IL-35 and PSA were assessed using the enzyme-linked immunosorbent assay (ELISA) in serum. RESULTS: All parameters showed significant differences between prostate cancer subjects and control, with higher PSA level in prostate cancer subjects (10.2±2.8 ng/mL). AR, PAP, IL-8, IL-35, and CTLA-4 were independently associated with PSA level in predicting prostate cancer progression (p<0.05). However, after multivariable analysis, only PAP, IL-8, and CTLA-4 had shown overall association with PSA serum, which all three show positive correlation. CONCLUSION: After integrated model analysis, only PAP, IL-8, and CTLA-4 remained significantly associated with PSA levels, indicating that combination of PSA, PAP, IL-8, and CTLA-4 levels might account for a substantial proportion of progression and biochemical activity in prostate cancer patients, and may serve as potential combined biomarker. KEYWORDS: interleukin-35, prostate cancer, interleukin-8, prostate-specific antigen, testosterone
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) coexists with diabetes mellitus and presents a significant therapeutic challenge due to its complex metabolic and hepatic pathology. Insulin therapy remains the cornerstone for glycemic management, but its effects on hepatic steatosis is inconsistent. Complementary therapies are needed to address this limitation. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) secretome has emerged as therapeutic approach for metabolic disease due to its anti-inflammatory, immunomodulatory, and antioxidant properties. This study was conducted to evaluate whether adjunctive administration of UC-MSCs secretome could enhance therapeutic outcomes, particularly in alleviating hepatic steatosis in a diabetic MASLD rat model. METHODS: Male rats were grouped into normal and diabetic MASLD rat model, and treated with either growth medium, insulin, UC-MSCs secretome, or combination of insulin and UC-MSCs secretome for 4 weeks. Blood samples were collected and liver enzymatic and lipid profile were analyzed using chemistry analyzer. Liver tissue was also obtained for assessment of liver fibrosis using Hematoxylin-Eosin staining, interleukin (IL)-6 measurement using enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity measurement using colorimetry. RESULTS: Combined insulin and UC-MSCs secretome therapy showed a trend toward better blood glucose management and lipid parameters, although not statistically significant. Administration of insulin, secretome, and their combination was associated with higher hepatic SOD levels and lower IL-6 protein levels, although not statistically significant. Combined therapy also reduced hepatomegaly compared to untreated diabetic MASLD rat model, and improved hepatic steatosis while significantly alleviating fibrosis severity. CONCLUSION: Combination of insulin and UC-MSCs secretome therapy in diabetic MASLD was able to improve several parameters related to hepatic steatosis compared with the untreated diabetic MASLD rat model. These findings suggest that UC-MSCs secretome might serve as a potential adjunct to insulin therapy. KEYWORDS: metabolic dysfunction-associated steatotic liver disease, type 2 diabetes, cell free therapy, umbilical cord mesenchymal stem cells, secretome
BACKGROUND: Colorectal cancer (CRC) is a major global health problem associated with high cancer-related mortality. Profiling of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status has become a decisive predictive biomarker in the management of CRC. However, KRAS mutation testing is commonly performed using tumor tissue obtained through invasive biopsy or surgery; therefore, fecal DNA analysis might offer a promising non-invasive alternative. This study was conducted to evaluate the concordance of KRAS mutations between matched tumor tissue and fecal samples and their association with clinicopathological characteristics. METHODS: This cross-sectional study included 94 patients confirmed of CRC. Tumor tissue specimens were obtained during surgical resection or biopsy, while fecal samples were collected pre-operatively. KRAS mutations were analyzed using polymerase chain reaction (PCR) and DNA sequencing, and the associations with clinicopathological variables were statistically evaluated. RESULTS: KRAS mutations were detected in 45.74% of tumor tissue and 26.60% of fecal samples. The overall concordance rate was 65.96%, with a Cohen’s Kappa of 0.291 (95% CI: 0.110–0.472), indicating "fair agreement". Notably, allele-specific concordance was 100% among double-positive cases. The fecal assay demonstrated 41.86% sensitivity, 86.27% specificity, 72.00% positive predictive value (PPV), and 63.77% negative predictive value (NPV). Tumor location (colon versus rectum) was significantly associated with fecal KRAS detection (p=0.028); other variables showed no significant association (p>0.05). CONCLUSION: KRAS mutations were more frequently detected in tissue than in fecal samples, with fair agreement. High allele-specific concordance suggests fecal DNA accurately reflects the tumor's mutational profile. Tumor location significantly influences DNA detectability, supporting fecal-based KRAS testing as a potential non-invasive approach for CRC molecular assessment. KEYWORDS: colorectal neoplasms, feces, KRAS protein, human, mutation, neoplasm tissue
BACKGROUND: Adults with central obesity may develop impaired fasting glucose (IFG) due to chronic low-grade inflammation. Although C-reactive protein (CRP) is a common marker of systemic inflammation, it is nonspecific and cannot fully capture obesity-related inflammatory pathways. Netrin-1 promotes macrophage retention in visceral adipose tissue, thereby sustaining inflammation and insulin resistance, while platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) reflect complementary inflammatory pathways; however, their discriminatory performance and associations with IFG remain uncertain. Therefore, this study was conducted to evaluate these markers in adults with central obesity. METHODS: Blood samples from 88 adults with central obesity were obtained, and fasting glucose concentration was measured using hexokinase method to determine IFG status. Serum Netrin-1 was measured using an enzyme-linked immunosorbent assay (ELISA), serum CRP was measured using fluorescence immunoassay (FIA); PLR and MLR were calculated from complete blood counts. Receiver operating characteristic (ROC) analysis assessed discriminatory performance, while exploratory logistic regression adjusted for age, sex, and BMI to examine biomarker associations with IFG. RESULTS: Among 88 participants, 54.5% had IFG. The AUCs were 0.694, 0.627, 0.689, and 0.532 for Netrin-1, PLR, MLR, and CRP, respectively. In crude prevalence-ratio (PR) analysis, Netrin-1 ≥315.35 pg/mL (PR=1.742; p=0.006), PLR ≥132.43 (PR=1.593; p=0.019), and MLR ≥0.20 (PR=2.119; p<0.001) were associated with IFG, whereas CRP was not. In separate ROC analysis, MLR had an AUC of 0.689 (p=0.002). After adjustment for age, sex, and BMI; MLR ≥0.20 remained associated with IFG (adjusted OR=7.516; p<0.001). CONCLUSION: Elevated serum Netrin-1, PLR, and MLR were associated with IFG in adults with central obesity. MLR showed the strongest crude association and was the only evaluated inflammatory biomarker retained in the exploratory adjusted logistic regression model. As an inexpensive index derived from a routine complete blood count, MLR may complement fasting-glucose assessment by helping characterize the inflammatory phenotype of adults with central obesity. KEYWORDS: central obesity, C-reactive protein, impaired fasting glucose, netrin-1, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio
BACKGROUND: Triple-negative breast cancer (TNBC) progression is driven by dysregulation of multiple interconnected signaling pathways rather than a single molecular abnormality, but current treatment strategies TNBC primarily rely on single-target therapy, highlighting the need for therapeutic candidates that may target multiple signaling pathway of TBNC. Tiliroside, a naturally occurring flavonoid glycoside, has demonstrated promising anticancer activity; however, its predicted effects on TNBC-associated oncogenic signaling networks remain poorly understood. Therefore, this study aimed to investigate the predicted molecular mechanisms by which tiliroside may modulate TNBC-associated oncogenic signaling networks. METHODS: Integrated computational approach combining network pharmacology, comparative molecular docking, and induced-fit docking was employed. Potential targets of tiliroside were predicted using SwissTargetPrediction and intersected with TNBC-associated genes retrieved from GeneCards. Protein–protein interaction and KEGG pathway enrichment analyses were performed to identify key molecular targets and signaling pathways. Comparative molecular docking was subsequently conducted using 19 structurally related flavonoids with reported anticancer activities against the identified hub proteins, followed by induced-fit docking to characterize the binding mechanism of tiliroside. RESULTS: Fifteen overlapping targets were identified between tiliroside and TNBC. Network analysis highlighted Akt serine/threonine kinase 1 (AKT1), sarcoma (SRC), and epidermal growth factor receptor (EGFR) as the principal hub genes, while the KEGG enrichment revealed significant involvement of phosphoinositide 3-kinase (PI3K)–AKT, erythroblastic leukemia viral oncogene B (ErbB), EGFR tyrosine kinase inhibitor resistance, focal adhesion, and vascular endothelial growth factor (VEGF) signaling pathways. Tiliroside consistently exhibited one of the most favorable binding profiles among the evaluated flavonoids, with binding energies of −9.41, −8.62, and −8.25 kcal/mol toward AKT1, SRC, and EGFR, respectively. Induced-fit docking further confirmed stable hydrogen-bond and hydrophobic interactions within the active sites of these proteins. CONCLUSION: Tiliroside exerts potential anti-TNBC activity through multitarget modulation of interconnected oncogenic signaling pathways, suggesting that tiliroside might be a promising lead compound for TNBC. KEYWORDS: tiliroside, triple-negative breast cancer, network pharmacology, induced-fit docking
BACKGROUND: Osteomalacia is a bone metabolic disease resulting from inadequate mineralization due to vitamin D deficiency and disturbances in calcium and phosphate metabolism. To date, information on the combined assessment of traditional markers of mineral metabolism and bone turnover biomarkers in patients with osteomalacia remains scarce. Therefore, the present investigation was conducted to assess the diagnostic value of biochemical and bone turnover markers for osteomalacia and to identify the potential gender-specific differences. METHODS: This case–control study included 100 subjects with osteomalacia and 100 healthy controls. Blood samples were collected, and serum levels of calcium, phosphate, and alkaline phosphatase (ALP) were measured using chemistry analyzer; vitamin D were and parathyroid hormone (PTH) were measured using immunofluorescence; while procollagen type 1 N-propeptide (P1NP), C-terminal telopeptide (CTX) and sclerostin level were measured using enzyme linked immunosorbent assay (ELISA). The diagnostic utility of the evaluated biomarkers was then subsequently assessed. RESULTS: Serum calcium, phosphate, and vitamin D were significantly reduced, while ALP and PTH concentrations were increased in osteomalacia subjects compared to control (p<0.001). Sclerostin concentrations were significantly higher in osteomalacia subjects than controls (p<0.003), especially in females than in males (p=0.021). P1NP levels were significantly altered in osteomalacia subjects compared with controls (p<0.001). Biochemical profiles were comparable across genders, except for sclerostin, which was significantly higher in females (p=0.021) and lower T-scores compared with males. BMI increased significantly with age (p=0.024). ROC analysis showed strong discriminatory ability of evaluated biomarkers within the study population. CONCLUSION: Elevated sclerostin and P1NP levels were associated with osteomalacia and may be useful biomarkers reflecting impaired bone formation, improving diagnostic accuracy when used alongside conventional markers. Sclerostin concentrations were considerably higher in female patients than in males, suggesting possible sex-related differences in bone metabolism. KEYWORDS: sclerostin, vitamin D, osteomalacia, mineralization, bone turnover biomarkers
BACKGROUND: Transforming growth factor β1 (TGF-β1) is a major mediator of myocardial fibrosis and cardiac remodeling in hypertension. TGFB1 (rs1800470) and MTHFR (rs1801133) are known for their roles in TGF-β1 regulation and cardiovascular remodeling, with MTHFR rs1801133 potentially influencing TGF-β1–mediated fibrosis through homocysteine metabolism. However, genetic determinants and relationship of these polymorphism with left ventricular (LV) structure remain unclear in the Indonesian population. Clarifying these associations may improve risk stratification and precision care. Therefore, this study was conducted to assess the associations of these polymorphisms and TGF-β1 levels with LV remodeling in essential hypertension. METHODS: Sixty-four adults subjects with essential hypertension were included in this cross-sectional study, and their blood samples were taken. Genotyping of the MTHFR and TGFB1 genes was performed using polymerase chain reaction (PCR), followed by sequencing. Serum TGF-β1 was measured by enzyme-linked immunosorbent assay (ELISA), while LV mass index (LVMI) and relative wall thickness (RWT) were assessed by echocardiography. RESULTS: TGFB1 rs1800470 was significantly associated with higher TGF-β1 levels (p=0.013). In the recessive model, TT homozygotes had higher TGF-β1 than CC+CT carriers (β=1.444; standardized β=0.353; p=0.004). TGF-β1 correlated with LDL cholesterol and diastolic blood pressure (r=0.302; p=0.015 and r=0.277; p=0.027). The TT genotype was associated with higher RWT under recessive and overdominant models (p=0.021 and p=0.028). CONCLUSION: TGFB1 rs1800470 is associated with circulating TGF-β1 concentrations in essential hypertension, suggesting a potential role in hypertensive cardiac remodeling. KEYWORDS: hypertension, TGFB1 polymorphism, TGF-β1, cardiac remodeling, left ventricular geometry, myocardial fibrosis.
BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by progressive periodontal tissue destruction and dysregulated inflammatory responses. Current therapies mainly target bacterial infection but are often less effective in controlling inflammation. Tea (Camellia sinensis) contains bioactive polyphenols with antimicrobial and anti-inflammatory properties, making it a promising alternative therapeutic candidate. However, molecular interactions of tea-derived compounds with inflammation-related proteins through molecular docking remain unclear. This study evaluate the binding affinity and interaction profiles of tea-derived compounds with inflammation-related to periodontitis protein targets using molecular docking. METHODS: Ligand and protein structures were retrieved from public databases and prepared using standard optimization protocols. Toxicity and pharmacokinetic properties were predicted using ProTox-3.0 and SwissADME, respectively. Molecular docking was performed using CB-Dock 2.0 with AutoDock Vina, and ligand-protein interactions were analyzed using Discovery Studio. RESULTS: All tested compounds, including catechin, epigallocatechin gallate (EGCG), theaflavin, and thearubigin showed low predicted toxicity. Theaflavin showed the strongest binding affinity across multiple targets, particularly against IRAK-4 (−9.8 kcal/mol), TLR4 (−9.2 kcal/mol), and IKK-β (−9.5 kcal/mol), supported by stable hydrogen bonds and hydrophobic interactions. CONCLUSION: Among all compounds, theaflavin exhibit strong multi-target binding potential against key inflammatory proteins in periodontitis, followed by EGCG and thearubigin. These findings support their potential as alternative or adjunctive anti-inflammatory agents, although further in vitro and in vivo validation are required. KEYWORDS: periodontitis, tea polyphenols, theaflavin, molecular docking, inflammation, NF-κB pathway
BACKGROUND: Sleep is essential for children's growth and development, yet sleep disturbances remain common among preschoolers. Insufficient sleep has been linked to cognitive impairments, behavioral problems, and increased risk of obesity. Nutritional factors, particularly omega-3 fatty acids, may play a role in sleep regulation. Although previous studies have suggested that Eicosapentaenoic Acid (EPA) and Docosahexaenoic acid (DHA) are associated with improved sleep outcomes, yet data on omega-3 status and its relationship with sleep duration among Indonesian preschoolers remain scarce. Therefore, this study was conducted to analyse the association between Omega-3 fatty acids levels and sleep duration among preschool children in Indonesia. METHODS: A cross-sectional survey was conducted among 72 children aged 3-5 years old. Sleep duration and disturbances of subjects were assessed using the Children's Sleep Habits Questionnaire-Abbreviated (CSHQ-A). Omega-3 fatty acids levels, including alpha-linolenic acid (ALA), EPA, and DHA, were measures using gas chromatography. RESULTS: The median sleep duration was 11 hours (range 9-13.5 hours). Based on CSHQ-A scores, 93.1% of subjects experienced sleep disturbances. Mean total omega-3 fatty acid concentration was 225.47 +/- 80.9 & micro;mol/L. Significant positive corelations were observed between sleep duration and total omega-3 fatty acid (r=0.298; p=0.011), EPA (r=0.233; p=0.049), and DHA (r=0.260; p=0.028). CONCLUSION: Omega-3 fatty acid levels, particularly EPA and DHA, were positively associated with sleep duration in preschool children. These findings provide preliminary evidence of the role of omega-3 in sleep regulation and underscore the importance of considering nutritional factors in efforts to improve sleep quality during early childhood.
BACKGROUND: Intestinal tuberculosis (ITB) is a type of tuberculosis (TB) that affects the gastrointestinal tract. Cathelicidin, an antimicrobial peptide, contributes to defense against Mycobacterium tuberculosis, which causes TB. Its expression is tightly regulated by vitamin D through vitamin D receptor signaling and autophagy pathways. Despite the increasing evidence on TB, studies exploring the correlation between cathelicidin and vitamin D in the ITB remain poorly characterized and almost exclusively derived from pulmonary TB. Therefore, the present study was conducted to compare serum cathelicidin and vitamin D levels between subjects with ITB and without ITB, and to determine the correlation between these two biomarkers. METHODS: This comparative cross-sectional study utilized stored serum samples obtained from participants enrolled in a previous ITB project. Twenty-two ITB and 22 non-ITB subjects aged >18 years who had undergone colonoscopy, histopathological examinations, and fulfilled predefined clinical and diagnostic criteria were included. Serum cathelicidin and vitamin D levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA), respectively. RESULTS: Significantly higher levels of serum cathelicidin were identified in ITB subjects, with a median level of 3.67 (2.27-5.95) ng/mL, compared with non-ITB subjects with a median level of 2.04 (1.66-2.46) ng/mL (p<0.0001). Although the difference was not statistically significant (p=0.091), vitamin D level tended to be lower in subjects with ITB, with a median level of 11.05 (6.80-25.25) ng/mL, compared to non-ITB subjects with a median level of 17.95 (12.13-23.63) ng/mL. A significant moderate negative correlation was found between cathelicidin and vitamin D (r=-0.485, p=0.001). CONCLUSION: The ITB is associated with elevated cathelicidin levels and a tendency toward lower vitamin D levels. The inverse correlation suggests a complex relationship between vitamin D status and cathelicidin expression, highlighting immunological mechanisms involved in ITB pathogenesis.
BACKGROUND: Anterior uveitis is the most common form of intraocular inflammation and an important cause of visual morbidity worldwide. Human leukocyte antigen B27 (HLA-B27) is a well-established immunogenetic risk factor; however, its molecular diversity remains insufficiently characterized in Indonesian populations. This study was conducted to characterize HLA-B27 at both the serological and genetic levels by quantifying serum antigen levels and identifying sequence variations in the HLA-B27 gene associated with anterior uveitis in Indonesian patients. METHODS: Thirteen anterior uveitis patients who were clinically evaluated through the Standardization of Uveitis Nomenclature (SUN) criteria were involved in this study. Blood sample was collected from subjects, and serum HLA-B27 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Genomic DNAwas analyzed using combined Sanger and Oxford Nanopore sequencing. Variant calling and annotation were performed using a custom bioinformatics pipeline. RESULTS: Serum HLA-B27 antigen levels were significantly higher in anterior uveitis patients than in healthy reference controls. Sequence analysis identified 43 patient-exclusive variants after exclusion of shared polymorphic changes, from which 13 recurrent or potentially functionally relevant variants were prioritized for downstream analysis. These variants were predominantly distributed within exons 2 and 3 and comprised single-nucleotide substitutions, coding-region insertion-deletion events, and one promoter-region insertion. Several coding variants resulted in amino acid substitutions, while adjacent compensatory indel pairs were also identified among exon 2 frameshift-associated variants. CONCLUSION: Anterior uveitis is associated with both elevated circulating HLA-B27 antigen levels and sequence variation within functionally important regions of the HLA-B27 gene, particularly exons 2 and 3. The identified missense substitutions, coding-region indels, and promoter insertion suggest potential effects on peptide binding, molecular stability, immune interaction, intracellular protein handling, or transcriptional regulation.
BACKGROUND: Obesity is linked to chronic low-grade inflammation and increased oxidative stress that may disrupt hypothalamic metabolic homeostasis. Excess nutrient intake activates inflammatory signaling and promotes glial reactivity, contributing to neuroinflammatory remodeling. Superoxide dismutase (SOD) is a key enzymatic antioxidant marker reflecting hypothalamic defense capacity. However, whether natural antioxidants can simultaneously restore SOD activity and attenuate obesity-induced glial reactivity remains unclear. Among many natural antioxidant, Moringa oleifera is rich in bioactive compounds with antioxidant properties that may attenuate neuroinflammation. Therefore, this study was conducted to evaluated the effect of M. oleifera fruit extract (MOFE) on hypothalamic total SOD activity and histopathological features of glial reactivity in obese Wistar rats. METHODS: Male Wistar rats were divided into four groups: normal control, obese control, and two treatment groups. For obese control and treatment groups, obesity was induced for 8 weeks using a high-fat/high-sucrose diet. Fresh M. oleifera fruit pods were macerated to produce MOFE. Following the obesity-induction, the two treatment groups were treated with 500 and 1,000 mg/kgBW/day MOFE for 4 weeks. A hydroxylamine-based assay was employed to measure total SOD activity of hypothalamic tissue homogenate. Meanwhile, hematoxylin-eosin (HE) was used to stain hypothalamic sections for glial reactivity scoring. RESULTS: After the obesity induction, the obesity-induced rats showed elevated Lee Index, but after the treatment with 500 and 1,000 mg/kgBW/day MOFE, the Lee Index decreased for 26.61 +/- 3.53% and 26.32 +/- 0.93%, respectively, which is greater compared to obese control. MOFE administration was also able to improve hypothalamic SOD activity (64.75 +/- 1.29 U/mL and 65.78 +/- 0.74 U/mL). MOFE groups also exhibited predominantly milder histopathological changes and glial reactivity than obese controls. CONCLUSION: MOFE administration lowers Lee Index, improves hypothalamic SOD activity, reduces glial reactivity and improves neuroinflammation changes in obese rats, suggesting that MOFE might be potential agent for obesity-related oxidative-inflammatory brain injury.
BACKGROUND: Conventional antidiabetic drugs, while effective, are often associated with adverse effects, secondary failure, and high costs, particularly in developing countries. This has driven interest in complementary plant‑based therapies. Gynura procumbens is a medicinal plant traditionally used in Southeast Asia for diabetes and metabolic disorders, however scientific evidences supporting this use have not been elucidated well. In this study, G. procumbens leaf extract (GPLE) was assessed whether it could lower glucose, restore antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), reduce the oxidative marker malondialdehyde (MDA), suppress pro‑inflammatory cytokines such as interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, and improve pancreatic structure in diabetic rats. METHODS: Twenty eight male Wistar rats were divided into four groups: normal rats, untreated diabetic rats, and diabetic rats given 500 or 1000 mg/kg of GPLE orally for 14 days. Blood glucose, SOD, GPx, and MDA were measured by spectrophotometry, while IL‑6, IL‑8, and TNF‑α were measured by enzyme‑linked immunosorbent assay (ELISA). Pancreas sections were stained with H&E. RESULTS: Administration of both extract doses significantly lowered fasting blood glucose by approximately 66% relative to the untreated diabetic control group (p<0.05). The administration of 1000 mg/kg GPLE increased SOD activity by 107% and GPx activity by 488%, while reducing MDA by 95% (p<0.05). Proinflammatory cytokines were markedly suppressed IL‑6 by 76%, IL‑8 by 76%, and TNF‑α by 79% at the high dose. Histological examination showed that treated rats had nearly normal islet morphology, reduced vascular congestion, and almost no lymphocytic infiltration. CONCLUSION: GPLE demonstrates promising antihyperglycemic, antioxidant, and anti-inflammatory activities alongside structural pancreatic preservation in a preclinical model. These findings suggest its potential as a candidate for further exploration in complementary metabolic therapies. KEYWORDS: antioxidants, diabetes mellitus, Gynura procumbens, histopathology, inflammation, oxidative stress
BACKGROUND: Silver nanoparticles (AgNPs) are commonly synthesized by chemical methods; however, these methods often involve toxic chemicals that may limit their biomedical applications. In contrast, pulsed laser ablation in liquid (PLAL) is a clean and chemical-free technique capable of producing highly pure AgNPs. Yet, only limited studies have investigated the structural, optical, antibacterial, and cytotoxicity properties of AgNPs synthesized by PLAL. Therefore, this study was conducted to synthesize pure AgNPs using pulsed laser ablation and evaluate their biomedical activity against bacterial strains and MCF-7 cells. METHODS: The synthesis of AgNPs was done by PLAL technique, and the characterization of nanoparticles were further determined using transmission electron microscopy (TEM), X-ray diffraction (XRD), and Ultraviolet-Visible (UV–Vis) spectroscopy. Antibacterial activity of AgNPs was tested with agar well diffusion method and the cytotoxicity effect was evaluated with MTT assay against the MCF-7 cells. RESULTS: TEM analysis showed semi-spherical AgNPs with an average particle size of 31 nm. XRD analysis showed that the structure was crystalline face-centered cubic with an average crystallite size of 16.8 nm. Peak value of the SPR was recorded at 405 nm and the optical band gap was 2.28 eV. Concentration dependent antibacterial activity was observed for the AgNPs and inhibition zones of 17 mm against Streptococcus mutans and 18 mm against Lactobacillus spp. at highest concentration. Moreover, concentration-dependent cytotoxicity against MCF-7 cells was observed, reaching a maximum inhibition of about 69% at 1000 µg/mL and IC₅₀ of about 90 µg/mL. CONCLUSION: The synthesized AgNPs showed favorable structural and optical characteristics, along with antibacterial and cytotoxic activities. Both effects were concentration-dependent, indicating their potential for further biomedical applications. KEYWORDS: silver nanoparticles, laser ablation, antibacterial activity, MCF-7, cytotoxicity
BACKGROUND: Standard treatment for glioblastoma multiforme (GBM) chemotherapy with temozolomide (TMZ) is often limited by chemoresistance, which is correlated with cancer immune evasion caused by the dysregulation of natural killer group 2 member D ligands (NKG2DL). While suppression of NKG2DL facilitates cancer progression, how chemoresistance regulates NKG2DL expression remains unclear. This study was conducted to examine the association of TMZ resistance with the expression and secretion of the NKG2DL subtype, MHC class I chain-related protein B (MICB), in human GBM cells. METHODS: An experimental in vitro study was conducted using TMZ-sensitive (U87MG) and intrinsically TMZ-resistant (T98G) human GBM cell lines. MICB mRNA expression was analyzed via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Surface protein expression and extracellular secretion of MICB were measured using flowcytometry and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Repeated TMZ exposure successfully induced resistance in U87MG-R (+TMZ) cells, yielding significantly higher cell viability (p<0.01) and slower proliferation rates compared to parental U87MG cells. Following 2-days TMZ treatment, both intrinsically resistant T98G and adaptively resistant U87MG-R (+TMZ) cells, demonstrated a significant increase in MICB mRNA levels (p<0.05 and p<0.0001, respectively) and extracellular secretion of soluble MICB protein (p<0.01 and p<0.01, respectively), compared to TMZ-sensitive counterparts. Conversely, MICB surface protein level after 2-days TMZ treatment was significantly reduced in both T98G (p<0.0001) and U87MG-R (+TMZ) (p<0.01) cells relative to the respective U87MG cells. CONCLUSION: GBM cell resistance to TMZ was associated with an upregulation of MICB mRNA transcription and extracellular protein secretion, and concurrently with a suppression of MICB expression on the cell surface. These conditions may lead to a cellular adaptive mechanism to develop resistance to TMZ and may represent a strategic route to evade native host immune.
