Current Pharmaceutical Design - Online First

Immunomodulatory disorders, such as autoimmune diseases, inflammatory conditions, and viral infections, stem from immune system dysregulation and often resist conventional therapies. Stem cells, particularly mesenchymal (MSCs) and hematopoietic stem cells (HSCs), possess immunomodulatory and regenerative properties, offering a promising therapeutic alternative.

A systematic literature review was conducted using databases, including PubMed, Scopus, Web of Science, and Google Scholar, for studies published between 1996 and 2025. A total of 287 articles were screened, and 132 were selected based on relevance, quality, and focus on stem cell biology, immunoregulatory mechanisms, and therapeutic applications.

Stem cells demonstrated significant capacity to regulate immune responses, suppress the production of inflammatory cytokines, enhance regulatory T-cell populations, and promote tissue regeneration. HSCs are effectively used in hematologic malignancies and immune reconstitution, while MSCs show promise in treating conditions, such as rheumatoid arthritis, diabetes mellitus, and influenza-induced lung injury. Emerging evidence also supports the role of cancer stem cells (CSCs) in targeted cancer therapies.

Stem cells offer a mechanism-driven approach to restoring immune balance and repairing tissue damage. However, variability in clinical outcomes, ethical concerns, and safety risks, such as tumorigenesis, limit their translation into clinical practice. Advances in cell derivation, immunomodulatory profiling, and delivery systems are critical to optimizing outcomes.

Stem cell-based therapies represent a paradigm shift in the treatment of immunomodulatory disorders by addressing the root cause of immune dysfunction. Continued research, ethical oversight, and clinical validation are crucial for transitioning stem cell therapy into routine medical practice.

Citrus reticulata (CR) has a long-standing role in traditional medicine, primarily due to its bioactive constituents such as hesperidin and narirutin, which are known for their antioxidant, anti-inflammatory, antibacterial, and anticancer properties.

This study investigates the anti-proliferative activity of CR water extracts against DU-145 prostate cancer cells and explores the therapeutic potential and underlying molecular mechanisms of hesperidin and narirutin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) through network pharmacology and molecular docking approaches.

Cytotoxicity assays were employed to determine the anti-cancer efficacy (IC50) of processed CR water extracts in DU-145 cells. Targets related to hesperidin, narirutin, PCa, and BPH were identified using bioinformatics platforms. Network pharmacology was applied to construct compound-target interaction networks and perform enrichment analyses (GO, KEGG, and DisGeNET) to elucidate key signalling pathways. Molecular docking was conducted to validate compound-target interactions.

Soil-processed CR extracts exhibited the strongest anti-cancer activity (IC50 = 1.789 mg/mL). Enrichment analyses identified significant pathways, including AGE-RAGE signalling, p53 signalling, inflammation, angiogenesis, and apoptosis. Molecular docking confirmed strong binding affinities of hesperidin and narirutin to the predicted targets.

Based on in vitro assays and in silico analyses, processed Citrus reticulata peel extracts may exert beneficial effects in both prostate cancer and benign prostatic hyperplasia. The soil-processed water extract demonstrated the most significant potential. The results suggest that the major compounds may act on several key proteins and pathways related to apoptosis and inflammation. However, further experimental and in vivo studies are needed to confirm their efficacy and safety.

Anti-proliferative assays, network pharmacology, and molecular docking collectively demonstrate that hesperidin and narirutin from CR show strong therapeutic potential against PCa and BPH. The findings highlight the involvement of AGE-RAGE and p53 signalling pathways and support the potential of these compounds in future drug development.

The current study aimed to synthesize and identify the biological activities of pyrazine-piperidine amide pharmacophore derivatives against non-small lung carcinoma (Calu-6) cells.

The combinatorial formulation was prepared by an active mixture of different chemical substituents, and five (6A-E) different molecules were synthesized. The chemical structures were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance (H1) spectroscopy.

These compounds were also screened for cytotoxicity against the Calu-6 cell line. Compounds 6B and 6D displayed potent cytotoxicity, with IC50 Values of 45.21 µM and 89.64 µM, respectively. Cellular uptake and apoptotic studies using compound microscopy and flow cytometry revealed that cell damage gradually increased, leading to cell death. Compound 6B at 25 µM and 50 µM had 75.3% and 65.3% viability, 8.61% and 9.85% apoptotic effects, 12.05% and 21.4% late apoptosis, and 4.02% and 3.4% necrosis, respectively.

Compound 6B was found to significantly enhance cell cycle arrest at the G2/M phase. Additionally, real-time RT-PCR and western blot analyses further confirmed the enhanced expression of apoptotic markers, such as caspase-3 and 8, as well as the antiproliferative gene p53.

These findings indicate that compound 6B has a promising anticancer effect on lung cancer.

3D bioprinting is a rapidly evolving technology in healthcare, especially in the fields of regenerative medicine, pharmaceutical research, and tissue engineering. This technique utilizes bioinks to fabricate three-dimensional structures that replicate the architecture and function of natural tissues through layer-by-layer additive manufacturing. This review aims to explore the current advancements, challenges, and future directions of 3D bioprinting.

A comprehensive review of the literature was conducted, focusing on various approaches to 3D bioprinting, including biomimicry, scaffold-based, scaffold-free, autonomous self-assembly, organ-on-a-chip, and microtissue building block techniques. Additionally, advancements in bioink development and different bioprinting technologies such as inkjet, extrusion, laser-assisted, stereolithography, acoustic, and magnetic bioprinting were analyzed.

The literature highlights significant progress in bioprinting technologies, demonstrating the transition of 3D bioprinting from a theoretical innovation to a practical tool in tissue engineering and regenerative medicine. Advances in printing precision, cell-material interactions, and bioink formulations are bringing the technology closer to clinical applications.

Key challenges remain—most notably creating robust vascular networks, scaling up production without loss of function, and ensuring that engineered tissues integrate seamlessly with a patient’s own biology. Still, the potential payoffs are enormous, from tailor-made implants and on-demand drug testing platforms to fully functional organ replacements.

3D bioprinting stands poised to transform personalized medicine and regenerative therapies. Achieving this vision will require sustained, interdisciplinary efforts to refine printing methods, innovate bioink chemistry, and master tissue maturation.

Obesity represents a significant health and lifestyle issue worldwide. White and brown adipocytes, which originate from resident mesenchymal stem cells (MSCs), are critically involved in the process of adipogenesis.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) were utilized to investigate epigenetic modifications associated with adipogenic differentiation. Briefly, histone acetylation and/or methylation pattern of hUCMSCs were evaluated with histone deacetylase inhibitor Trichostatin A (TSA) for cell viability, death rate, and adipogenic commitment.

Inhibition of histone deacetylation was accompanied by a reduction of the global methylation pattern compared to the baseline levels in untreated cells. These changes decreased cell viability at 36 hrs, while reciprocally increasing the rate of cell death from 24 hrs. Most importantly, TSA-treated cells demonstrated diminished adipogenic differentiation compared to normal cells post-induction.

Epigenetic remodeling triggered by inhibition of histone deacetylase led to reduced DNA methylation. The increased cytotoxicity, impairing cell survival due to alteration in chromatin state, reduced adipogenic differentiation potential in TSA-treated cells, promoting disruption of normal lineage commitment pathways.

Taken together, the results show a possible anti-obesity effect of histone deacetylation inhibitors (HDCAs) in MSCs, resulting in depletion and restriction of their adipogenic differentiation.

For centuries, Traditional Chinese Medicine has been a subject of extensive research for its healing properties, including its effects against viruses. The pollen of Typha angustifolia emerges as a notable natural source of antiviral agents, with earlier investigations focusing on its antioxidant and anti-inflammatory properties, which are associated with flavonoids and phenolics that facilitate electron transfer. These bioactive compounds could potentially disrupt viral entry and replication, thereby necessitating further studies.

Molecular docking analysis was conducted on 11 compounds from T. angustifolia targeting the entry protein of dengue virus, the NS5B polymerase of hepatitis C virus, and the RdRp of Japanese encephalitis virus. The binding affinity was evaluated through LibDock score assessments, and simulations of molecular dynamics (RMSD and RMSF) were performed to analyze the stability of the complexes.

Naringenin was consistently identified as one of the highest binders for all three viral proteins, achieving the top score for the RdRp of Japanese encephalitis (129.288). Isorhamnetin showed the greatest binding affinity for the hepatitis C NS5B polymerase (120.827), exceeding that of sofosbuvir (120.629), while isorhamnetin-3-O-rutinoside displayed strong binding to the dengue viral entry protein (97.0838). Molecular dynamics confirmed the stability of ligand-protein interactions, underlined by sustained van der Waals and electrostatic forces.

These findings underscore naringenin as a versatile antiviral candidate, with other flavonoids exhibiting specific effectiveness that could facilitate multitarget inhibition approaches. This polypharmacological potential of flavonoids aligns with their established antiviral properties, although confirmatory experimental studies are critical.

Naringenin emerged as the most potent and reliable antiviral agent among the compounds of T. angustifolia, particularly against the RdRp of Japanese encephalitis. These computational insights validate T. angustifolia pollen as a promising natural antiviral resource, warranting further validation through in vitro and in vivo studies.