Current Pharmaceutical Design - Volume 30, Issue 35, 2024

Fufang Banmao capsule (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data.

The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredient- target-pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC.

FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinical data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69.

Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

Previous studies have reported the benefit of statins after heart transplant (HT). However, the use of high-dose statins might be limited in some HT patients due to intolerance and interactions with immunosuppression or might not be enough to achieve low-density lipoprotein (LDL) cholesterol goals. Hyperlipidemia has been associated with coronary allograft vasculopathy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors might be a safe and effective option in HT patients with suboptimal lipid control.

In a retrospective study, we identified HT patients in our center with LDL cholesterol >100 mg/dL, after diet modifications and up-titration of statins to maximum tolerated dose, treated with PCSK9i. The primary endpoint was LDL reduction one month after, and secondary endpoints were the development of donor-specific HLA antibodies (DSA) and the presence of coronary allograft vasculopathy or rejection.

From January, 2018, to January, 2024, we identified five HT patients treated with PCSK9 inhibitors. In all cases, evolocumab was used. A significant reduction in LDL cholesterol was observed (151.6 ± 13.5 mg/dl to 72.4 ± 14.6 mg/dl; p = 0.04, mean reduction 75.7 ± 14.1 mg/dl), as well as in total cholesterol (231 ± 34.6 mg/dl to 152.2 ± 38.9 mg/dl; p < 0.01, mean reduction 78.8 ± 22.2 mg/dl). A significant increase in HDL cholesterol was not observed (45.4 ± 10.9 mg/dl to 46.2 ± 11.1 mg/dl; p = 0.60). One patient developed DSA five years after treatment onset. Rejection and coronary allograft vasculopathy were not observed.

PCSK9 inhibitors are safe and effective in reducing LDL in HT patients. However, larger studies are needed to clarify if they can reduce the development of coronary allograft vasculopathy.

As cancer therapy progresses, challenges remain due to the inherent drawbacks 
of conventional treatments such as chemotherapy, gene therapy, radiation therapy, and surgical removal. Moreover, due to their associated side effects, conventional treatments affect both cancerous and normal cells, making photodynamic therapy (PDT) an attractive alternative.

As a result of its minimal toxicity, exceptional specificity, and non-invasive characteristics, 
PDT represents an innovative and highly promising cancer treatment strategy using photosensitizers (PSs) and precise wavelength excitation light to introduce reactive oxygen species (ROS) in the vicinity of cancer cells.

Poor aqueous solubility and decreased sensitivity of Rhodamine 6G (R6G) prevent its use as a photosensitizer in PDT, necessitating the development of oxidized sodium alginate (OSA) hydrogelated nanocarriers to enhance its bioavailability, targeted distribution, and ROS-quantum yield. The ROS quantum yield increased from 0.30 in an aqueous environment to 0.51 when using alginate-based formulations, and it was further enhanced to 0.81 in the case of OSA.

Furthermore, the nanoformulations produced fluorescent signals suitable for use as cellular 
imaging agents, demonstrating contrast-enhancing capabilities in medical imaging and showing minimal toxicity.

Silver nanoparticles (AgNPs) have gained significance due to their practical use in the medicinal field, especially in the treatment of tumors and cancer. The current article explores a green synthetic method for the preparation of AgNPs using leaf extract of Euphorbia royleanas.

The synthesis was conducted at different parameters like concentration of AgNO3, pH, salt concentration, temperature and time to optimize best results for their biochemical applications. It was validated through UV-V spectroscopy (400-450 nm) with 1:3 (concentration ratio of leaf ethanolic extract and 1 mM AgNO3 solution) at a pH value of 8 at 35°C, which were the best optimization conditions. The FTIR spectral bands showed the presence of C-N and ^–OH functional groups, indicating that ^–OH stretching and the aliphatic -C-H stretching were involved in the reduction of Ag ions. The XRD pattern showed the face-centered cubic structure of silver nanoparticles. The results of SEM revealed that AgNPs were predominantly spherical in shape, mono-dispersed, and arranged in scattered form. EDX analysis testified the presence of metallic silver along with other elements like Cl, C, and O.

The investigation of biochemical parameters showed that AgNPs were influential in the discoloration of dye wastewater (methylene blue), where 80% of dye color was removed in 20 min, followed by the significant (p < 0.05) analgesic activity with an inhibition percentage of 86.45% at a dose of 500 mg/kg.

Similarly, the antioxidant activity with the highest percent inhibition was 55.4% (p < 0.0001), shown by the AgNPs at 500 µg/mL. AgNPs showed a 30 mm zone of inhibition at 100 µl/mL against Aspergillus niger. It was concluded that AgNPs provide a baseline in medical technology for the treatment of simple to chronic diseases.