Dipeptidyl peptidase-IV (DPP-IV) inhibition is a validated therapeutic mechanism for type 2 diabetes mellitus. Marine-derived bioactive peptides offer a diverse array of potential inhibitors but often exhibit pharmacokinetic limitations that impede clinical translation. This study aimed to identify and evaluate candidate peptides from Arbacia lixula as potential DPP-IV inhibitors using an integrated in silico approach. A total of twenty peptides were evaluated in silico for absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles using SwissADME, pkCSM, and ProTox. Molecular docking against DPP-IV was performed in MOE v2022.02 with linagliptin as the reference ligand; docking poses were evaluated by predicted binding energy and root mean square deviation (RMSD). Top-ranked peptide-DPP-IV complexes were subjected to 50 ns molecular dynamics (MD) simulations in YASARA Dynamics v4.3.13 to assess conformational stability. ADMET predictions showed low gastrointestinal absorption in most peptides, whereas Peptides 17, 18, and 20 showed high predicted absorption. No target-organ or endpoint-specific toxicity was predicted. Peptides 7, 15, and 18 were prioritized based on favorable docking scores, RMSD <2.0 Å, and relevant DPP-IV residue interactions. Docking scores were interpreted cautiously, not as direct quantitative comparisons with linagliptin. During 50 ns MD simulations, RMSD, root mean square fluctuation, radius of gyration, and solvent-accessible surface area profiles supported the stability, compactness, and dynamic consistency of selected peptide-DPP-IV complexes. Peptides 7, 15, and 18 showed favorable in silico predicting binding, relevant DPP-IV interactions, and acceptable preliminary safety profiles as potential DPP-IV inhibitory candidates. These findings should be interpreted as computational leads that require further in vitro and in vivo validation.
Bridelia ovata Decne. is a Thai traditional medicinal plant whose pharmacognostic standards, validated analytical methods, and anticancer mechanisms against triple-negative breast cancer (TNBC) remain unreported. The objective of this study was to establish a pharmacognostic monograph for B. ovata leaves, validate a high performance liquid chromatography (HPLC) method for epigallocatechin (EGC) quantification, profile the extract by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), and investigate signal transducer and activator of transcription 3 (STAT3)-mediated anti-proliferative mechanisms in MDA-MB-231 TNBC cells. One authenticated and 14 commercial B. ovata leaf samples were evaluated by macroscopic and microscopic examination, thin-layer chromatography fingerprinting, phytochemical screening, physicochemical analysis, validated HPLC, LC-QTOF-MS profiling, network pharmacology, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and Western blotting. Key diagnostic features included paracytic stomata, lignified fibers, and calcium oxalate crystals. Most physicochemical parameters met World Health Organization general guidelines. The HPLC method showed excellent linearity (r 2 > 0.9995; 20-500 μg/mL); EGC content ranged from 0.20 to 11.05% w/w. LC-QTOF-MS tentatively identified 24 metabolites spanning phenolic acids, catechins, flavonoid glycosides, and terpenoids. Furthermore, network pharmacology identified STAT3 as the key hub target. B. ovata extract selectively inhibited MDA-MB-231 viability (IC50 = 413 ± 23 μg/mL vs. IC50 > 800 μg/mL in MCF-10A), induced G2/M arrest, and suppressed p-STAT3 (Tyr705) and cyclin D1 expression in a dose-dependent manner. These findings integrate pharmacognostic identification, physicochemical standardization, and mechanistic evidence of STAT3 pathway modulation, collectively supporting B. ovata as a phytopharmaceutical candidate for TNBC. B. ovata leaves demonstrate reproducible pharmacognostic identity, consistent EGC-based chemical quality markers, and STAT3-mediated antiproliferative activity, warranting further preclinical investigation.
There is an escalating demand to identify novel bioactive compounds from medicinal plants due to the increasing number of antifungal-resistant pathogenic microorganisms. This study aimed to evaluate the antifungal activities of Moringa oleifera Lam. (MoLm.) leaves and the potential of its chemical constituents against Candida albicans, by inhibiting lanosterol-14-α-demethylase and (1,3)-β-D-glucan synthase, via molecular docking. This was an in vitro and in silico study. n-hexane, ethyl acetate, and methanol fractions were obtained from MoLm. leaves, with concentrations ranging from 10% to 50% (w/v) used to determine the zone of inhibition (ZoI), minimum inhibitory concentrations (MICs), and minimum fungicidal concentrations (MFCs). C. albicans strain ATCC 10231 was used. Three hundred chemical constituents were obtained from MoLm. fractions were obtained through liquid chromatography-mass spectrometry analysis, and echinenone, L-α-palmitin, betaine, α-linolenic acid, 2-pyrrolidone, curcumene, cinnamic acid, and methyl cinnamate were docked to lanosterol-14-α-demethylase and (1,3)-β-D-glucan synthase. The largest ZoI was observed in 10% ethyl acetate and 20% methanol fractions at 11.5 and 9 mm, respectively. The MICs of all fractions were within the range of 2.5%-5%, while only the n-hexane fraction showed an MFC of 10%. Echinenone had the strongest binding energy toward the enzymes, at -13.35 and -10.57 kcal/mol, and had the best Ki value of 1.65 × 10-4 and 1.8 × 10-2 μM, respectively. The docking results indicate that the chemical constituents were derived from MoLm. leaf fractions exhibit strong binding affinity toward critical molecular targets in C. albicans, suggesting their potential to disrupt essential cellular processes and contribute to antifungal activity.
Kretek smoke contains various toxic substances that are harmful to human health and has been associated with inflammation and structural alterations in multiple organs. However, its effects on cardiac tissue remain incompletely understood. This study aimed to evaluate myocardial histopathological alterations and p53 protein expression following subchronic kretek smoke exposure in rats. Male Rattus norvegicus Sprague-Dawley rats were randomly divided into two groups. Group I was exposed to normal air, while Group II was exposed to kretek smoke at a dose of 1 kretek/rat/day for 30 days. Cardiac tissues were examined using H&E and MT staining. IHC analysis was performed to assess myocardial p53 protein expression, while ultrastructural observations of the myocardium were conducted using SEM. Group II rats exhibited myocardial inflammation characterized by lymphocyte infiltration and increased collagen accumulation, whereas Group I rats showed no inflammatory changes and minimal collagen deposition. Myocardial p53 protein expression was significantly higher in Group II (224.68 ± 5.44 µm²) than in Group I (199.87 ± 13.35 µm²; P = 0.005). Ultrastructural myocardial alterations were observed in Group II but not in Group I. In conclusion, subchronic kretek smoke exposure increases myocardial p53 protein expression accompanied by inflammatory and fibrotic alterations.
A natural O/W sunscreen based on lignosulfonate, olive leaf extract, and propolis was developed. Formulations were evaluated for physicochemical properties, antioxidant and antibacterial activities, and sun protection factor (SPF). Results showed physical stability over 28 days with particle sizes of 2-28.53 μm and viscosities of 28-51 poise. The L3E3P10 formulation exhibited the highest SPF of 34.32. This phenolic combination synergistically enhances photoprotection.
The extract of Rhizophora mucronata leaves has demonstrated potential anti-inflammatory activity. Its fractions may exhibit enhanced activity due to the presence of more specific metabolites. This research was performed to determine the anti-inflammatory activity and characterize the R. mucronata leaf fractions using Fourier-transform infrared (FTIR) spectroscopy integrated with chemometric analysis. This was an experimental in vitro study evaluating the anti-inflammatory activity of R. mucronata leaf fractions and characterizing their chemical profiles using FTIR and liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The ethanol extract was fractionated using vacuum liquid chromatography. The anti-inflammatory activity was evaluated by measuring the inhibition of egg albumin denaturation in the sample. The fractions were characterized using FTIR spectroscopy combined with chemometrics. The secondary metabolite profile of the fraction with the highest anti-inflammatory activity was examined using LC-HRMS. The FTIR profile of R. mucronata leaves was analyzed using principal component analysis (PCA) and hierarchical cluster analysis. Fraction N has the highest percentage of egg albumin denaturation inhibition activity. Naringin and ferulic acid were the most abundant flavonoid and phenolic compounds detected in fraction N. FTIR spectra indicated variations in chemical composition among fractions. In the PCA biplot, fraction N was closely aligned with the variable at 1376 cm-1, indicating strong C-H bending of methyl groups. Fraction N demonstrated the ability to inhibit egg albumin denaturation. Nevertheless, further investigation is necessary to confirm these results.
Traditionally used to treat inflammatory diseases, Kaempferia galanga L. includes bioactive substances with anti-inflammatory properties, such as eugenol and ethyl p-methoxycinnamate. Its potential as a topical treatment for wound healing is yet unclear, though. This study aims to assess the ability of K. galanga cream (KGC) in accelerating wound healing and to observe its effects on excisional wound models based on plasma levels of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α). Six groups (n = 5) were created from thirty male Wistar rats. After creating a 1.5-cm full-thickness wound on the dorsal side, without treatment as a control, a base cream as a negative control, 10% povidone-iodine cream as a positive control, or KGC (5%, 10%, or 15%) was applied topically every day for 14 days. On days 7 and 14, the ImageJ software was used to quantify the wound area. Plasma TNF-α and IL-10 levels were measured on day 15 using enzyme-linked immunosorbent assay, and statistical evaluation was conducted via one-way analysis of variance with Tukey's post hoc test. KGC markedly improved wound healing versus the negative control. The 10% formulation produced the greatest effect, reducing wound area by 65.3% on day 14 (P < 0.001). It also markedly decreased TNF-α levels by 38.7% (P < 0.001) and increased IL-10 levels by 42.5% (P < 0.001) compared with the negative control. The 10% KGC demonstrated the most effective wound healing activity, likely through modulation of pro- and anti-inflammatory cytokines. These findings support its potential as a topical herbal formulation for wound management.
Vitamin K1 intake is an important modifiable factor in dietary counseling for warfarin patients; however, region-specific food composition data in Thailand are limited. This small compositional pilot study aimed to determine Vitamin K1 concentrations in five commonly consumed indigenous vegetables from Upper Northern Thailand and to summarize estimated Vitamin K1 intake under predefined portion-size scenarios. Fresh vegetable samples were collected from local markets in Phayao Province and analyzed by the high-performance liquid chromatography with fluorescence detection. Estimated Vitamin K1 intake was modeled for three consumption scenarios (100, 300, and 1200 g/day) and compared to a benchmark intake of 150 μg/day from the literature. The concentration of Vitamin K1 ranged from 71.3 to 212.5 μg/100 g fresh weight, with Gymnema inodorum having the highest concentration. The 100 and 300 g/day scenarios were used as primary descriptive scenarios, whereas the 1200 g/day scenario was retained only as a conservative sensitivity analysis. These findings should be interpreted as descriptive intake estimates relevant to dietary counseling and not as evidence of altered anticoagulation outcomes. Data on the Vitamin K1 composition of different regions may help to provide more locally adapted dietary advice for patients taking warfarin.
Difficult in vitro fertilization (IVF) cases involving both immature oocytes and immotile sperm remain a clinical challenge. This study evaluated embryo quality in a mouse model using pentoxifylline (PTX)-treated sperm and calcium ionophore (CaI)-matured oocytes. This was an experimental study using a mouse model. The immotile sperms were supplemented by PTX, while the immature oocytes were incubated with CaI. Then, the conventional IVF was performed to unite both germ cells. The development of the embryos was observed on days 1 and 3, respectively. Data were analyzed using SPSS. Oocyte maturity was compared between the groups using the Chi-square test. Sperm motility and embryo quality were analyzed using the Kruskal-Wallis test, followed by the Mann-Whitney post hoc test for pairwise comparisons. In this study, the maturation process was found more frequently with the addition of CaI (45.3%), and the motility of spermatozoa was also increased with the addition of PTX (31%). The quality of embryos after adding CaI and PTX (1st day - 58.3% and 3rd day - 33.3%) was significantly different from that without addition, although it was not different when compared to adding CaI alone or PTX alone. We conclude that in a mouse model, the addition of calcium for immature oocytes and PTX for immotile spermatozoa may assist in difficult cases in IVF practices, even though further research is needed, particularly in a clinical trial in human.
Skin aging is a biological process, characterized by wrinkle formation, loss of elasticity, and decreased hydration. It is influenced by intrinsic and extrinsic factors, including ultraviolet (UV) exposure, pollution, and oxidative stress. This study developed a topical formulation combining bergamot essential oil (EOBs) and virgin coconut oil within an ionic gel system, encapsulated in nanostructured lipid carriers (NLCs), aiming to provide anti-aging, moisturizing, and UV-protective benefits. The GEOBs-VNLCs ionic gel formulation was prepared using a gelation method that combined sonication with dropwise stirring, followed by encapsulation within an NLC matrix via heating and homogenization, involving the formation of lipid and aqueous phases. The GEOBs-VNLCs formulation exhibited an average particle size of 140 ± 1.79 nm, low polydispersity (0.24 ± 0.02), negative zeta potential (-31.93 ± 1.17 mV), skin-compatible pH (5.13 ± 0.12), and high encapsulation efficiency (69.20 ± 0.57%), indicating good physicochemical stability for topical application. The formulation demonstrated moderate antioxidant activity (Half-maximal inhibitory concentration 7.39 μg/mL; 0.288 mg AAE/g dw), negligible improvement in skin hydration (P > 0.05), and low photoprotective performance (sun protection factor 8.12; PA+). The GEOBs-VNLCs formulation shows potential as a multifunctional, natural-based skincare system with antioxidant, moisturizing, and mild photoprotective properties.
Dairy products may influence bone metabolism through calcium bioavailability and modulation of gut microbiota. This study compared the effects of yogurt and ultra-high-temperature (UHT) milk on serum osteocalcin and calcium levels in rats. Twenty-four male Wistar rats (Rattus norvegicus) were randomly assigned to control, UHT milk, and yogurt groups (n = 8 each) and administered the intervention for 8 weeks. Serum osteocalcin was measured at weeks 4 and 8, and serum calcium was measured at week 8. At week 4, both UHT milk and yogurt groups demonstrated significantly higher osteocalcin levels than the control group. A significant difference was also observed between the UHT milk and yogurt groups (P = 0.046). At week 8, osteocalcin levels remained significantly higher in both intervention groups than in the control group (P < 0.001), whereas no significant difference was detected between the UHT milk and yogurt groups (P = 0.674). Serum calcium levels were also significantly higher in the intervention groups than in the control group (P < 0.001), with higher levels observed in the yogurt group than in the UHT milk group (P = 0.037). Yogurt and UHT milk were associated with increased serum osteocalcin and calcium levels in rats. Yogurt was associated with earlier increases in circulating osteocalcin levels and higher serum calcium levels, whereas both dairy products demonstrated comparable osteocalcin levels after 8 weeks. These findings reflect changes in circulating biochemical markers associated with bone metabolism rather than direct evidence of enhanced bone formation or skeletal structural improvement.
Adequate wound healing is important for re-establishing the normal skin function. Determining the most suitable therapeutic strategy for skin repair involves multiple considerations, including wound type and condition, injury severity, lesion extent, and exudate level. Mitragyna speciosa (M. speciosa) is prominent for its therapeutic benefits and wound-healing properties. Nanostructured lipid carriers (NLCs) have proven beneficial for the M. speciosa extract, due to the restricted biocompatibility of active compounds in M. speciosa leaves. This study is the first to showcase the potential of M. speciosa leaf extract encapsulated in NLCs in a hydrogel for wound healing in rat models. M. speciosa leaf extract-encapsulated NLCs (MS-NLC) in hydrogel film can enhance wound recovery in rat models by facilitating faster wound contraction and promoting tissue repair in a shorter period as new growth tissue was visible at the peripheries of the abrasion observed from Day 3, hydroxyproline levels on day 21 was significantly higher than day 6 and day 15 (P > 0.05), and the reading of tumor growth factor-beta 1 (TGF-β1) through quantitative-polymerase chain reaction results on day 6 further revealed upregulation particularly in the 1000 mg/mL hydrogel group, reflecting active fibroblast function and tissue repair. TGF-β1 signaling is involved in key wound healing processes and could facilitate wound recovery observed with the MS-NLC hydrogel film, supporting its potential as a novel wound healing approach. However, the absence of a vehicle control limits the ability to attribute the observed effects solely to the active extract.
Staphylococcus aureus infections, particularly methicillin-resistant S. aureus (MRSA), remain a major clinical challenge due to limited treatment options. Plant-derived compounds have gained interest as alternative or adjunct antibacterial agents. This study investigated the antibacterial, antibiofilm, and synergistic effects of Terminalia arjuna extract against S. aureus and MRSA, with high-performance liquid chromatography (HPLC) analysis. Antibacterial activity of T. arjuna extract was evaluated using microdilution, time-kill, checkerboard, and biofilm assays against S. aureus and MRSA, with chemical profiling by HPLC. Data were calculated and shown as means ± standard deviation. A Significant difference was marked when P < 0.05. The ethanolic extract of T. arjuna demonstrated bactericidal action against S. aureus and MRSA, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration values of 625 μg/mL. A concentration-dependent effect was observed, with complete bacterial killing achieved at supra-MIC levels. The extract reduced biofilm biomass by more than 80% at low concentrations. Notably, a pronounced synergistic interaction with ampicillin against MRSA was observed, yielding a fractional inhibitory concentration index of 0.281. The T. arjuna extract exhibited in vitro antibacterial activity and showed concentration-dependent bactericidal effects, with a synergistic interaction with ampicillin observed against MRSA.
Colorectal cancer (CRC) remains a global health challenge. The efficacy of 5-fluorouracil (5-FU) is frequently limited by chemoresistance, inflammation, and compensatory pro-angiogenic signaling. Prebiotic fibers and metabolically active lipids have been shown to modulate immune-metabolic pathways that may influence tumor behavior and chemotherapy response. The aim of the study was to evaluate the immunomodulatory and chemo-adjunct effects of inulin, glucomannan, and a combined inulin-glucomannan-medium-chain triglyceride (MCT) formulation on CRC cells exposed to 5-FU. An in vitro experimental study using human colorectal adenocarcinoma HT-29 cells. HT-29 cells were exposed to graded concentrations of inulin, glucomannan, or their combination with MCT, either as single treatments or combined with 5-FU. Outcomes included MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based viability, clonogenic survival, and vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) expression using immunocytochemical (ICC). Data differences were analyzed using one-way analysis of variance with Tukey's post hoc test or the Kruskal-Wallis test with Dunn's post hoc test, as appropriate. Inulin increased short-term metabolic activity and partially attenuated 5-FU-induced cytotoxicity, whereas glucomannan demonstrated minimal effects. MCT supplementation further enhanced metabolic activity, indicating differential nutrient-chemotherapy interactions. The combined inulin-MCT-glucomannan formulation exerted the most consistent long-term effects, significantly reducing colony formation and modulating VEGF and IL-6 expression in a dose-dependent manner. However, VEGF increased at higher concentrations. The triple-component formulation modulated proliferative capacity and inflammatory-angiogenic signaling and altered cellular responses to 5-FU, supporting a modulatory rather than uniformly sensitizing role in CRC cells.
Cimetidine, an H2 receptor antagonist with anti-androgenic disrupts testicular structure and spermatogenesis. Anthocyanins in red onion (Allium cepa) have good antioxidant and cytoprotective action. This study compared the protective ability of onion-derived anthocyanin extract on the cimetidine-induced testicular toxicity in male mice, with respect to spermatogenic integrity, endocrine regulation, histopathology, and pharmacodynamic dose-response relationships. Sixty-four adult albino mice (male) were placed in control, anthocyanin (25-300 mg/kg), cimetidine (20 mg/kg), and cimetidine + anthocyanin (combinations) groups. Treatments were done in the form of intraperitoneally during 38 days. The assessment was done on testicular histology, seminiferous tubular diameter, germinal epithelium thickness, spermatogenic cell populations, Johnsen scores, daily sperm production, and Leydig cell indices. Anthocyanin co-treatment (25-300 mg/kg) produced a dose-dependent protective effect, with near-normal histological structure observed at 250-300 mg/kg. Daily sperm production increased significantly, showing a leftward shift in dose-response (ED50: 45.7 mg/kg vs. 57.9 mg/kg for anthocyanin alone). Onion anthocyanins exert potent, dose-dependent protective effects against cimetidine-induced testicular toxicity by preserving spermatogenesis and endocrine homeostasis, supporting their translational potential as fertility-protective adjuncts during gonadotoxic drug exposure.
Sterculia coccinea Jack (hantap) is an Indonesian medicinal plant with limited evidence of anticancer activity. The objective of this study was to identify the phytochemical components of hantap leaf extract, evaluate its interaction with estrogen receptor-alpha (ER-α) through molecular docking, and develop nanoliposome formulations to improve its physicochemical properties. The extract yield was 15.7%, and the phytochemical profile was characterized using liquid chromatography-high-resolution mass spectrometry. Molecular docking against ER-α was performed using tamoxifen as the reference ligand. Nanoliposomes were prepared by thin-film hydration using phosphatidylcholine and cholesterol at ratios of 0.6:0.3 (F1), 0.9:0.3 (F2), and 1.2:0.3 (F3). The formulations showed particle sizes of 158.3 ± 1.59 nm, 148.23 ± 2.68 nm, and 157.3 ± 1.10 nm; zeta potentials of - 30.16 ± 1.40 mV, -31.61 ± 0.16 mV, and - 32.84 ± 0.31 mV; and polydispersity index values of 0.28 ± 0.02, 0.29 ± 0.03, and 0.23 ± 0.02 for F1, F2, and F3, respectively. Entrapment efficiency for total phenolics ranged from 94.43% to 97.04%, while total flavonoid entrapment ranged from 32.84% to 73.54%. Docking analysis showed that linarin and apigenin had stronger binding affinity to ER-α than tamoxifen. Based on physicochemical evaluation, F2 was selected as the optimal formulation and showed weak cytotoxic activity against Michigan Cancer Foundation-7 (MCF-7) cells in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, with an IC50 value of 282.06 ± 3.39 μg/mL. In conclusion, hantap leaf extract nanoliposomes exhibited favorable nanoscale characteristics, while their cytotoxic effect against MCF-7 cells remained weak under the tested conditions.
A rising worldwide health concern, inflammatory bowel disease is linked to western-style diets that damage intestinal barrier integrity, change gut microbiota, and increase colonic inflammation. In contrast, inulin and glucomannan enhance short-chain fatty acid production and preserve mucosal structure, suggesting a protective role against diet-induced colonic inflammation. This study aimed to investigate whether combined inulin and glucomannan supplementation prevents western diet-induced colonic inflammation by modulating intestinal barrier function and colonic inflammatory cytokine profiles. Over 8 weeks, elicited by a high-fat, high-sucrose (HFHS) diet, colonic inflammation in mice as a model was utilized in a preventative experimental investigation. Mice received an HFHS diet with supplementation of inulin, glucomannan, or their combination. Colonic histopathology was evaluated, and interleukin 6 (IL-6) and IL-10 levels were assessed using immunohistochemistry. Statistical analyses included one-way analysis of variance with appropriate post hoc tests, covariate-adjusted analyses controlling for caloric intake, and correlation analyses between histological and inflammatory parameters. Fiber supplementation reduced HFHS-induced colonic inflammation severity, crypt shortening, and mucosal thinning without affecting caloric intake. While colonic inflammation severity linked favorably with IL-6 and inversely with IL-10 and mucosal integrity, combined inulin-glucomannan supplementation provided the lowest IL-6/IL-10 ratio along with uniquely elevated IL-10 expression, indicating better immunomodulatory effects. Soluble fiber supplementation prevents HFHS-induced colonic inflammation by preserving mucosal architecture and restoring inflammatory cytokine balance, with combined inulin and glucomannan providing additive immunoprotective benefits.
The Spatholobus littoralis Hassk. wood (SLW) is traditionally used for various ailments, including as anticancer. The study aimed to examine SL wood compounds as anticancer agents through the apoptosis mechanism mediated by the p38 mitogen-activated protein kinase (3HEG) with an in silico approach. Ten SLW compounds were chosen based on structure similarity with sorafenib. The ligands and receptor were prepared with Discovery Studio Visualizer (DSV), while AutoDockTools were used to examine the ligand–receptor binding. The method was validated to obtain binding affinity values (ΔG). The interactions and pharmacokinetic profiled with DSV and ADMETLab 3.0. The results showed that the ΔG’s of SLW compounds were in range -1.74 to -0.10 kcal/mol, compared to sorafenib − 10.50 kcal/mol. The molecular visualization revealed hydrophobic bond interactions between formononetin and p38’s residues on TYR182, LYS118, and VAL183. Among SLW’s compounds, the formononetin’s pharmacokinetic analysis indicated favorable bioavailability and Lipinski’s rule compliance. These findings suggest that flavonoid formononetin has promising potential as a p38 kinase inhibitor, although further work is needed to demonstrate its efficacy.
Chronic kidney disease (CKD) in children necessitates the use of a variety of drugs to reduce disease progression and manage complications. Polypharmacy is common in children with CKD, which can increase the occurrence of harmful drug interactions. This study aimed to evaluate drug prescribing patterns and their association with mortality in pediatric CKD patients at X Hospital Jakarta, using disease stage as a critical variable. This retrospective observational study examined 124 children with CKD from January 2020 to December 2024. The correlation among mortality, polypharmacy, and CKD stage was assessed by bivariate analysis (Spearman test). Lexicomp and Stockley’s Drug Interactions analyzed drug interactions. Survival analysis was performed using Kaplan–Meier curves and Cox regression. The study results showed that the population was predominantly male (52.4%) and aged 13–16 years (33.06%), with 70.16% of patients having CKD Stage G5. Prescribed drugs included antihypertensives, antibiotics, anemia treatments, and immunosuppressants. The majority of medication interactions (89.4%) were classified as moderate in severity. Although polypharmacy was highest in Stage G5, the correlation test revealed no significant relationship between CKD stage and polypharmacy (Spearman’s coefficient, 0.105; P = 0.247). There were 14 deaths in total, with 10 of them occurring in Stage G5. However, survival analysis (log-rank P = 0.987; Cox regression P = 0.988) demonstrated no statistically significant difference in mortality risk among the CKD stages. This study highlights that, despite a greater number of fatalities in Stage G5, the survival models did not show a statistically significant relationship between CKD stage and mortality, nor between CKD stage and polypharmacy.
Dental pulp stem cell (DPSC) has gained attention as a cell-free therapeutic approach to enhance bone regeneration. However, the degradation of exosomal biomaterials limits their application, which may be overcome by using an injectable chitosan hydrogel crosslinker (ICHC) as a natural polymeric carrier. ICHC was prepared and loaded with exosomes derived from DPSCs. Cytotoxicity, calcium deposition, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM) were conducted to assess biocompatibility, mineralization capacity, and structural characteristics. The cell viability of ICHCs, exosome 5 ng/mL, and exosome-loaded ICHC 0.6% ranged from 95% to 132%. NTA analysis revealed particle sizes of 147.5 nm for exosomes and 377.5 nm for exosome-loaded ICHC, with concentrations of 4.6 × 106 and 1.4 × 107 particles/mL, respectively. TEM further validated effective encapsulation, revealing electron-dense particles dispersed throughout the ICHC hydrogel matrix. The combination of exosome-loaded ICHC achieved 100% viability in osteoblast cells and promoted more elongated cell morphology compared to the control, suggesting a safe and effective cell-free material for bone regeneration therapy.
