Skin aging is one of the degenerative processes influenced by tyrosinase, elastase, collagenase, hyaluronidase, and matrix metalloproteinase-9 (MMP9) activity. One promising avenue for discovering antiaging therapeutics is the peptides from the Arbacia lixula spine. The aim of this study was to explore the potential of peptides from A. lixula spine as a multitarget inhibitor for recombinant antiaging therapies through in silico approaches. The crystal structure of peptides previously identified in A. lixula spine was visualized using the UCSF Chimera. The protein data bank (PDB) database was used to obtain the crystal structures of protein targets. The webservers Innovagen, AllerTop, and ToxinPred were utilized to predict the peptide's water solubility, toxicity, and allergenicity. MOE application was used to prepare all ligands and proteins, molecular docking, and visualization. Molecular dynamics simulations were carried out on the protein-ligand complexes on Yasara Dynamics application. The Benchling website was used to perform virtual electrophoresis and reconstruct the recombinant plasmid (Psb1c3). Based on the molecular docking results, peptide REGSPDLLE has the potential as a multitarget inhibitor of tyrosinase (-9.07 kcal/mol), hyaluronidase (-10.57 kcal/mol), elastase (-9.32 kcal/mol), collagenase (-10.57 kcal/mol), and MMP9 (-10.43 kcal/mol). Peptide REGSPDLLE was selected due to its strong binding affinity on the active site of each target protein and exhibits non-toxic, non-allergenic, and good water-soluble as indicated by Support Vector Machine score <0. Molecular dynamics simulations confirmed stable interactions with receptor proteins. Peptide REGSPDLLE was successfully inserted into the recombinant pSB1C3 plasmid, confirmed by virtual electrophoresis with bands at ~2000 bp and ~150 bp. Further in vitro and in vivo studies are necessary to verify the anti-aging efficacy of peptide REGSPDLLE.

Diabetic kidney disease is a condition characterized by persistent albuminuria, diabetic glomerular lesions, and a reduced glomerular filtration rate in people with diabetes. Peptides in Cucumaria frondosa coelomic fluid have been proven to provide antidiabetic and anti-inflammatory activity that can be used as one of the innovations in developing a multitarget therapy, especially in diabetic kidney disease. Therefore, the aim of this study was to unravel the power of peptide-based metabolites from C. frondosa coelomic fluid as multitarget therapy for diabetic kidney disease using an in-silico study. UCSF Chimera software was utilized to construct the three-dimensional structure of coelomic fluid peptides from C. frondosa. The toxicity and allergenicity of peptides were examined using the ToxinPred and AllerTop websites, respectively. From the PDBJ database, the 3D structures of protein kinase B, alpha isoform (AKT1); vascular endothelial growth factor receptor 2 (VEGFR2); epidermal growth factor receptor (EGFR); α-glucosidase; and glucokinase were obtained. Molecular docking was carried out using MOE Software. In this in-silico study, peptide 9 (-10.32 kcal/mol), peptide 1 (-9.41 kcal/mol), and peptide 3 (-9.55 kcal/mol) were shown to act as specific adenosine triphosphate-competitive inhibitors of EGFR, AKT1, and VEGFR2, respectively. Peptide 8 (-11.06 kcal/mol) can specifically inhibit α-glucosidase by binding to its active site. Peptide 1 (-9.80 kcal/mol) is predicted to specifically inhibit glucokinase activity by blocking its active side. Molecular dynamics simulations confirmed stable interactions with receptor proteins. In conclusion, C. frondosa coelomic fluid peptides have been shown not only to alleviate diabetic kidney disease but also to stabilize blood glucose levels and prevent hyperglycemia based on in-silico analysis.

Context: Placenta accreta spectrum (PAS) is an abnormal pregnancy condition that contributes significantly to maternal mortality and morbidity. Approximately 50-67% of PAS cases are undiagnosed before delivery. Therefore, there is an urgent need to find biomarkers that can be used for early detection so that PAS interventions can be provided promptly to reduce maternal mortality. Aims: To evaluate the diagnostic accuracy of microRNAs (miRNAs) as biomarkers of PAS. Methods: A literature search was conducted based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). The search was conducted on several databases, including PubMed and ScienceDirect. The risk of bias in the included articles was assessed based on the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A random-effects model was used to calculate sensitivity, specificity, positive-likelihood ratio (PLR), negative-likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). The subgroup analysis was carried out to investigate the heterogeneity. Deeks' funnel plot and Fagan's nomogram were used to evaluate the publication bias clinical application of miRNAs as a PAS diagnostic biomarker, respectively. Results: Based on three included studies involving 165 PAS cases, the pooled sensitivity, specificity, PLR, NLR, DOR, AUC were 0.90 (95% CI: 0.82-0.95), 0.85 (95% CI: 0.79-0.89), 7.24 (95% CI: 5.42-9.06), 0.33 (95% CI: 0.20-0.46), 72.06 (95% CI: 49.27-94.85), and 0.92 (95% CI: 0.90-0.94). Subgroup analysis showed that using cluster and upregulated miRNA enhances the diagnostic power of miRNA. There is no publication bias in this study (p=0.52). Conclusions: This study highlights the superior diagnostic accuracy of miRNAs in diagnosing PAS, indicating their potential as valuable biomarkers for detecting PAS.

Context: Colorectal cancer (CRC) remains a significant global health challenge despite advances in treatment modalities. The coelomic fluid of Lytechinus variegatus emerges as a rich source of bioactive peptides with the potential as a new therapeutic anticancer agent. Aims: To analyze the toxicity, allergenicity, and potential of L. variegatus coelomic fluid peptides as multitarget inhibitor agents of CRC cancer cells through an in silico study. Methods: Ten peptides from L. variegatus coelomic fluid were processed using UCSF Chimera software to model the three-dimensional structure. ToxinPred and AllerTop web servers were used to analyze the toxicity and allergenicity of peptides, respectively. The 3D structures of EGFR, AKT1, GSK3B, VEGFR2, and JAK3 were retrieved from the PDBJ database. MOE Software was used to perform molecular docking. Results: Peptide 4 binds to the ATP binding pocket of GSK3B protein with the strongest binding affinity value (-8,68 kcal/mol). The docking results between EGFR and peptides showed that peptide 10 binds to the ATP binding pocket with the lowest binding affinity (-9.52 kcal/mol). Peptide 2 binds to the ATP binding pocket of AKT1 with the lowest binding affinity value (-9.16 kcal/mol). Peptide 3 has the lowest binding affinity value of the JAK3 ATP binding pocket (-8,67 kcal/mol). Peptide 7 binds to the ATP binding pocket of VEGFR2 with the strongest binding affinity (-9,67 kcal/mol). Conclusions: The L. variegatus peptides have the potential as multitarget anti-CRC agents by inhibiting the activity of GSK3B, EGFR, AKT1, JAK3, and VEGFR2 proteins through the ATP competitive inhibitor action based on in silico study.

Introduction: Breast cancer remains a prevalent global malignancy and necessitates a treatment regimen, which is often accompanied by substantial side effects. To address this challenge, alternative therapies with fewer adverse effects are urgently needed. Amomum cardamomum has displayed promising anticancer potential. This study aimed to investigate the impact of A. cardamomum seed on T47D breast cancer cell viability and the ability to induce apoptosis, utilizing in silico and in vitro approaches. Methods: The samples were extracted utilizing the maceration method using ethanol 96% solvent. In addition, the bioactive constituents were identified through phytochemicals and GC/MS analysis. Cell viability was assessed through MTT assay at various concentrations with 24 and 48-hour incubation periods and compared with the control cells. Apoptosis patterns were visualized by Immunofluorescence assay and analyzed utilizing ImageJ software. In silico analyses included three distinct tests, namely pharmacokinetics analysis (ADMET), bioactivity prediction (PASS), and molecular docking. Results: The A. cardamomum seed extract inhibited the growth of the cells with an IC50 value of 97.28 μg/mL in 48 hours of the incubation period. Immunofluorescence assay exhibited that the extract induced apoptosis in over 50% of T47D cells. In silico approaches identified bicyclogermacrene, Germacrene-D, and δ-cadinene as potential JAK3, BRAF v600e, and MMP9 protein inhibitors. These compounds exhibited stronger binding affinities to critical amino acids than control ligands. Conclusion: This research presents compelling evidence that the A. cardamomum extract has anticancer activity against breast cancer by preventing growth and inducing apoptosis.

Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from Lytechinus variegatus spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD50) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from Lytechinus variegatus spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.