The coronavirus disease 2019 outbreak has become a huge challenge in the human sector for the past two years. The coronavirus is capable of mutating at a higher rate than other viruses. Thus, an approach for creating an effective vaccine is still needed to induce antibodies against multiple variants with lower side effects. Currently, there is a lack of research on designing a multiepitope of the COVID-19 spike protein for the Indonesian population with comprehensive immunoinformatic analysis. Therefore, this study aimed to design a multiepitope-based vaccine for the Indonesian population using an immunoinformatic approach. This study was conducted using the SARS-CoV-2 spike glycoprotein sequences from Indonesia that were retrieved from the GISAID database. Three SARS-CoV-2 sequences, with IDs of EIJK-61453, UGM0002, and B.1.1.7 were selected. The CD8+ cytotoxic T-cell lymphocyte (CTL) epitope, CD4+ helper T lymphocyte (HTL) epitope, B-cell epitope, and IFN-γ production were predicted. After modeling the vaccines, molecular docking, molecular dynamics, in silico immune simulations, and plasmid vector design were performed. The designed vaccine is antigenic, non-allergenic, non-toxic, capable of inducing IFN-γ with a population reach of 86.29% in Indonesia, and has good stability during molecular dynamics and immune simulation. Hence, this vaccine model is recommended to be investigated for further study.

Natural polymer-based hydrogels, generally composed of hydrophilic polymers capable of absorbing large amounts of water, have garnered attention for biomedical applications because of their biocompatibility, biodegradability, and eco-friendliness. Natural polymer-based hydrogels derived from alginate, starch, cellulose, and chitosan are particularly valuable in fields such as drug delivery, wound dressing, and tissue engineering. However, compared with synthetic hydrogels, their poor mechanical properties limit their use in load-bearing applications. This review explores recent advancements in the enhancement of the mechanical strength of natural hydrogels while maintaining their biocompatibility for biomedical applications. Strategies such as chemical modification, blending with stronger materials, and optimized cross-linking are discussed. By improving their mechanical resilience, natural hydrogels can become more suitable for demanding biomedical applications, like tissue scaffolding and cartilage repair. Additionally, this review identifies the ongoing challenges and future directions for maximizing the potential of natural polymer-based hydrogels in advanced medical therapies.

Context: Matrix metalloproteinases (MMPs) play a critical role in wound healing, with higher levels seen in chronic wounds, delaying healing. Since ancient times, propolis has been widely used for traditional wound healing. However, there is still limited research on MMP1 and MMP12. Aims: To evaluate new candidates of propolis compounds for targeting MMP1 and MMP12 using in silico studies supported by experimental screening using LC-MS/MS quadrupole-time of flight (QTOF). Methods: Compounds in propolis were screened using LC-MS/MS QTOF. The 3D structure of all compounds in propolis and protein targets was prepared in Autodock and Biovia Discovery Studio. The molecular docking of all compounds in propolis was carried out using Autodock on PyRx 0.9. Drug-likeness and ADMET analysis of selected compounds in propolis with the lowest affinity were observed. Lastly, molecular dynamic simulations of the best compounds in propolis were conducted using the GROMACS 2020 package. Results: Eleven flavonoid and phenolic compounds were identified in propolis using LC-MS/MS QTOF analysis. Molecular docking simulations showed that licoflavone A and pinostrobin exhibited the lowest binding affinity to MMP1 and MMP12, respectively. Molecular dynamic simulations revealed that licoflavone A formed a more stabilized complex with MMP1, while pinostrobin formed a more stabilized complex with MMP12 than the native ligand. Conclusions: This study revealed new candidates for MMP1 and MMP12 inhibitors from propolis compounds that can enhance wound healing. It is hoped that the evidence gathered in this study provides crucial new information in exploring new wound-healing medications.

Propolis contains a wide range of pharmacological activities because of their various bioactive compounds. The beneficial effect of propolis is interesting for treating type-2 diabetes mellitus (T2DM) owing to dysregulation of multiple metabolic processes. In this study, 275 of 658 Asian propolis compounds were evaluated as potential anti-T2DM agents using the DIA-DB web server towards 18 known anti-diabetes protein targets. More than 20% of all compounds could bind to more than five diabetes targets with high binding affinity (<−9.0 kcal/mol). Filtering with physicochemical and pharmacokinetic properties, including ADMET parameters, 12 compounds were identified as potential anti-T2DM with favorable ADMET properties. Six of those compounds, (2R)-7,4′-dihydroxy-5-methoxy-8-methylflavone; (RR)-(+)-3′-senecioylkhellactone; 2′,4′,6′-trihydroxy chalcone; alpinetin; pinobanksin-3-O-butyrate; and pinocembrin-5-methyl ether were first reported as anti-T2DM agents. We identified the significant T2DM targets of Asian propolis, namely retinol-binding protein-4 (RBP4) and aldose reductase (AKR1B1) that have important roles in insulin sensitivity and diabetes complication, respectively. Molecular dynamic simulations showed stable interaction of selected propolis compounds in the active site of RBP4 and AKR1B1. These findings suggest that Asian propolis compound may be effective for treatment of T2DM by targeting RBP4 and AKR1B1.

Cirrhosis naturally progresses through three stages: compensated, decompensated, and late decompensated, which carry an elevated risk of death. Although curcumin's anti-cirrhosis effects have been studied, underlying mechanism in preventing cirrhosis progression and the correlation between curcumin's action with upregulated genes remains insufficiently explored. In this study, we employed network pharmacology approach to construct a drug-target-disease network through bioinformatics and validate the findings with molecular docking and dynamic simulation. The curcumin-targeted liver cirrhosis network encompassed 54 nodes with 282 edges in protein-protein interactions (PPI) network. By utilizing network centrality analysis, we identified eight crucial genes. KEGG enrichment pathway revealed that these crucial genes are involved in pathway of cancer, endocrine resistance, estrogen signaling, chemical carcinogenesis-receptor activation, lipid metabolism, and atherosclerosis. Notably, these eight genes predominantly participate in cancer-related pathways. Further investigation revealed upregulation of four genes and downregulation of four others in hepatocellular carcinoma patients. These upregulated genes-MAPK8, SRC, PPARG, and HSP90AA1-strongly correlated with reduced survival probability in liver hepatocellular carcinoma patients with survival times approximately under 4000 days (∼11 years). Molecular docking and molecular dynamic results exhibited curcumin's superior binding affinities and stability compared to native ligands of MAPK8, SRC, PPARG, and HSP90AA1 within 50 ns simulations. Moreover, MM-GBSA analysis showed stronger binding energy of curcumin to MAPK8, SRC, and HSP90AA1 than native ligand. In conclusion, this study provides valuable insights into curcumin's potential mechanisms in preventing liver cirrhosis progression, specifically in HCC. These findings offer a theoretical basis for further pharmacological research into anti-HCC effect of curcumin.Communicated by Ramaswamy H. Sarma.

Objective: Hypertension is the leading contributor to all-cause death and disability worldwide. One of the most well-known first-line antihypertensive drugs is chlorthalidone which treats hypertension through carbonic anhydrase (CA) II inhibition. However, due to the high number of cases of hypertension, a more potent medication is still needed. Xanthone is a potential candidate for the compound group for its potency in inhibiting CA II. Therefore, this research aims to evaluate around 500 xanthones’ potency as a better oral antihypertensive drug than chlorthalidone. Methods: 507 xanthones were analyzed for their potency using in silico method. Xanthone’s structures were retrieved from the PubChem website or built using Avogadro software, while the CA II receptor was retrieved from The RCSB website. Then molecular docking, ADME evaluation, and toxicity test were evaluated from selected ligands. Finally, a molecular dynamics simulation was conducted to evaluate the stability of the potential ligand as the inhibitor of CA II protein. Results: This research found that globulixanthone c is considered to be a better CA II inhibitor compared to chlorthalidone. It is due to its lower binding affinity compared to chlorthalidone and its stable binding to CA II’s important inhibition sites with low fluctuation. It also has the potential to be consumed orally because it fulfills all of Lipinski's rule of five standards and its toxicity is on the moderate level. Conclusion: Globulixanthone c, a type of prenylated xanthones group, showed the best potential activity as the inhibitor of CA II protein to treat hypertension among other xanthones.