Hepatocellular carcinoma (HCC) has the highest mortality rate and is the most frequent of liver cancers. The heterogeneity of HCC in its etiology and molecular expression increases the difficulty in identifying possible treatments. To elucidate the molecular mechanisms of HCC across grades, data from The Cancer Genome Atlas (TCGA) were used for gene co-expression analysis, categorizing each sample into its pre-existing risk factors. The R library BioNERO was used for preprocessing and gene co-expression network construction. For those modules most correlated with a grade, functional enrichments from different databases were then tested, which appeared to have relatively consistent patterns when grouped by G1/G2 and G3/G4. G1/G2 exhibited the involvement of pathways related to metabolism and the PI3K/Akt pathway, which regulates cell proliferation and related pathways, whereas G3/G4 showed the activation of cell adhesion genes and the p53 signaling pathway, which regulates apoptosis, cell cycle arrest, and similar processes. Module preservation analysis was then used with the no history dataset as the reference network, which found cell adhesion molecules and cell cycle genes to be preserved across all risk factors, suggesting they are imperative in the development of HCC regardless of potential etiology. Through hierarchical clustering, modules related to the cell cycle, cell adhesion, the immune system, and the ribosome were found to be consistently present across all risk factors, with distinct clusters linked to oxidative phosphorylation in viral HCC and pentose and glucuronate interconversions in non-viral HCC, underscoring their potential roles in cancer progression.

Background/Objectives: Neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic Lateral Sclerosis (ALS) are clinically distinct but share overlapping molecular mechanisms. Methods: To identify conserved systemic signatures, we analyzed blood RNA-Seq datasets using Weighted Gene Co-Expression Network Analysis (WGCNA), differential expression, pathway enrichment, and miRNA–mRNA network mapping. Results: Two modules, the red and turquoise, showed strong preservation across diseases. The red module was enriched for cytoskeletal and metabolic regulation, while the turquoise module involved immune, stress-response, and proteostatic pathways. Discussion: Key hub genes, such as HMGCR, ACTR2, MYD88, PTEN, EP300, and regulatory miRNAs like miR-29, miR-132, and miR-146a, formed interconnected networks reflecting shared molecular vulnerabilities. The absence of classical heat shock proteins in preserved blood modules highlights tissue-specific expression differences between blood and neural systems. Several hub genes overlap with known pharmacological targets, suggesting potential in translational relevance. Conclusions: Together, these findings reveal conserved blood-based transcriptional modules that suggest parallel central neurodegenerative processes and may support future biomarker development and possible therapeutic exploration.

The fruit of Morinda citrifolia, also known as the noni tree, has been extensively used in Polynesian culture as an alternative medicine to various diseases. Recent studies have pointed out its anxiolytic activity in vitro and in mouse models. Despite the effectiveness of developed anxiolytic drugs in the market, the potential side effects of these medications have led people to resort to traditional medicine such as M. citrifolia. However, evidence regarding its anti-anxiety characteristics is still lacking to this day. Hence, this preliminary study implemented combined network pharmacology and molecular docking to validate its anti-anxiety claims. This study highlighted the bioactive compounds of the M. citrifolia fruit part to have excellent absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, particularly their outstanding oral bioavailability and blood–brain barrier penetration, both of which are essential considerations to ensure the effectiveness of anxiolytic drugs to arrive at the site of action. Moreover, noni fruit metabolites target genes involved in glutamatergic synapse pathways, which have been significantly associated with anxiety. Through molecular docking, selected compounds exhibited a strong binding affinity towards GRIA2 and PRKCA, both of which have connections with glutamatergic pathways. With all things considered, the results established that the noni fruit potentially contains therapeutic agents that elicit anti-anxiety potential. Through this, the promotion of a more sustainable, accessible, and affordable treatment of anxiety could be developed.

Berries from the Vaccinium genus, known for their rich array of bioactive metabolites, are recognized for their antioxidant, anti-inflammatory, and anticancer properties. These compounds, including anthocyanins, flavonoids, and phenolic acids, have attracted significant attention for their potential health benefits, particularly in cancer prevention and treatment. Gastric cancer (GC), a leading cause of cancer-related deaths worldwide, remains challenging to treat, especially in its advanced stages. This study investigates the therapeutic potential of Vaccinium species in GC treatment using computational methods. RNA sequencing revealed upregulated genes associated with GC, while network pharmacology and molecular docking approaches identified strong interactions between cyanidin 3-O-glucoside (C3G), a key bioactive metabolite. Furthermore, molecular dynamics simulations of the HSP90AA1-C3G complex demonstrated stable binding and structural integrity, suggesting that C3G may inhibit HSP90AA1, a protein involved in cancer progression. These findings highlight the therapeutic potential of Vaccinium metabolites, offering a novel approach to GC treatment by targeting key molecular pathways. This research provides valuable insights into the role of berries as natural therapeutics, supporting their integration into future gastric cancer treatment strategies.

Skin cancer, particularly melanoma, remains a major public health concern due to its high mortality rate. Current treatment options, including chemotherapy with dacarbazine and doxorubicin, have shown limited efficacy, achieving only a 20% objective response rate over six months, along with severe side effects such as cardiotoxicity. Given these limitations, there is a growing interest in herbal medicine as a source of novel anticancer compounds. Bambusa stenostachya, a bamboo species native to Taiwan, was investigated for its potential anti-melanoma properties using network pharmacology and molecular docking. LC-MS analysis identified seven bioactive compounds, including quinic acid and isovitexin, which satisfied Lipinski’s drug-likeness criteria. Among the seven bioactive compounds identified, five belong to the flavonoid family, while two are classified as phenolic compounds that modulate signaling pathways related to cancer and exhibit antioxidant activity, respectively. Through pathway enrichment analysis, four key melanoma-associated genes (PIM1, MEK1, CDK2, and PDK1) were identified as potential therapeutic targets. Ensemble docking results demonstrated that naringin-7-rhamnoglucoside exhibited the highest binding affinity (−6.30 kcal/mol) with phosphoinositide-dependent kinase-1, surpassing the affinities of standard chemotherapeutic agents. Additionally, the average docking scores for naringin-7-rhamnoglucoside and the remaining three proteins were as follows: PIM1 (−5.92), MEK1 (−6.07), and CDK2 (−5.26). These findings suggest that the bioactive compounds in B. stenostachya may play a crucial role in inhibiting melanoma progression by modulating metabolic and signaling pathways. Further in vitro and in vivo studies are necessary to validate these computational findings and explore the potential of B. stenostachya as a complementary therapeutic agent for melanoma.

Background/Objectives: The molecular heterogeneity and metabolic flexibility of Hepatocellular Carcinoma (HCC) pose significant challenges to the efficacy of systemic therapy for advanced cases. Early screening difficulties often delay diagnosis, leading to more advanced stages at presentation. Combined with the inconsistent responses to current systemic therapies, HCC continues to have one of the highest mortality rates among cancers. Thus, this paper seeks to contribute to the development of systemic therapy options through the consideration of HCC’s metabolic vulnerabilities and lay the groundwork for future in vitro studies. Methods: Transcriptomic data were used to calculate single and double knockout options for HCC using genetic Minimal Cut Sets. Furthermore, using QSAR modeling, drug repositioning opportunities were assessed to inhibit the selected genes. Results: Two single knockout options that were also annotated as essential pairs were found within the pyrimidine metabolism pathway of HCC, wherein the knockout of either DHODH or TYMS is potentially disruptive to proliferation. The result of the flux balance analysis and gene knockout simulation indicated a significant decrease in biomass production. Three machine learning algorithms were assessed for their performance in predicting the pIC50 of a given compound for the selected genes. SVM-rbf performed the best on unseen data achieving an R² of 0.82 for DHODH and 0.81 for TYMS. For DHODH, the drugs Oteseconazole, Tipranavir, and Lusutrombopag were identified as potential inhibitors. For TYMS, the drugs Tadalafil, Dabigatran, Baloxavir Marboxil, and Candesartan Cilexetil showed promise as inhibitors. Conclusions: Overall, this study suggests in vitro testing of the identified drugs to assess their capabilities in inducing pyrimidine starvation on HCC.