Kewalin Inthanon

Obesity poses a significant global health challenge, necessitating the search for novel therapeutic agents to address this epidemic. Chromenes, known for their diverse bioactivities, hold promise as potential anti-obesity compounds, yet research in this area remains limited. This pioneering study represents the first exploration of synthetic chromenes as potential anti-obesity agents, unveiling the underlying molecular pathways governing adipogenesis and lipolysis. Twenty-nine chromenes were synthesized using green chemistry approaches, resulting in five novel compounds: 1, 2, 3, 4, and 5. Among them, 14 chromenes demonstrated a lack of toxicity to pre-adipocytes (PAs) and mature adipocytes (MAs) of 3T3-L1 cells. The anti-adipogenesis and lipolysis enhancement potential of these non-toxic 14 chromenes were comprehensively evaluated using Oil Red O staining technique, LDH activity measurement, and glycerol release assays. Notably, 4, 5, 21 and 25 exhibited remarkable efficacy in reducing intracellular lipid accumulation without inducing cellular stress or cell death. Molecular analysis revealed significant alterations in the expression of key transcription factors involved in adipogenesis and lipid metabolism, including PPARγ, C/EBPα, ADD-1, Pref-1, IRS-1, GLUT-4, adiponectin, FAS, aP2, ATGL, and HSL. This suggests their potential role in anti-adipogenesis. Additionally, the treatments with 4 and 25 showed potential for enhancing lipolysis, providing further evidence of their anti-obesity properties. This study presents several promising prospects for the development of synthetic chromenes as potential anti-obesity agents, opening new avenues for drug discovery and benefitting individuals worldwide in addressing obesity-related challenges to human health. In addition, predictive in silico modeling was performed on the identified candidate chromenes. This modeling provides prospective anti-HIV activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these potential new chemical entities.

Novel biomaterials suitable for bone tissue engineering are currently in demand, and reformulating natural and synthetic biomaterials has caught scientists' attention. Cellulose and collagen have been utilized in biomedical fields. This research aimed to fabricate collagen‐cellulose‐poly(l‐lactide) (Col‐Cel‐PLL) scaffold using collagen, cellulose, and poly( l‐lactide) through electrospinning and radiofrequency plasma treatment and to examine the scaffold's physicochemical and biological properties. Fourier transform infrared spectroscopy revealed its chemistry, and scanning electron microscopy showed fine interconnecting microfibrous fibers; it was super‐hydrophilic with low crystallinity (25.59%) and great Young's modulus (163.940 ± 8.008 MPa), and it was reasonably degraded. Regarding biological properties, the scaffold was biocompatible by supporting cell attachment and viability. Cells on the Col‐Cel‐PLL produced high total protein levels and collagen deposition. However, the alkaline phosphatase activity was significantly low.

Reactive oxygen species (ROS) contribute to cancer growth and metastasis. Using antioxidants to modulate cellular ROS levels is a promisingstrategy for cancer prevention and treatment. Calophyllum inophyllum L., or tamanu, is a medicinal plant renowned for its anti-inflammatory, antioxidant, and anticancer properties in traditional medicine systems. However, the anticancer effects of C. inophyllum extract on cellular ROS remain unexplored. This study represents the first report on such effects and provides the potential mechanisms underlying the anticancer properties of C. inophyllum extract. The branches of C. inophyllum were extracted, and the extract was comprehensively analyzed for phytochemical constituents, antioxidant capacity, total phenolic content, and total flavonoid content. Subsequently, the extracts potential anticancer properties were evaluated using patient-derived cells from breast and lung cancer. The results revealed that the C. inophyllum extract possesses notable antioxidant activity and demonstrated no cytotoxicity within the initial 24h of treatment. However, after 72h, it exhibited significant antiproliferative effects. Moreover, the extract exhibited inhibitory properties against migration and invasion at concentrations below the IC₅₀, which corresponded to the expression of related genes. Notably, these effects correlated with the reduction of intracellular ROS levels. Overall, our findings highlight the anticancer potential of C. inophyllum extract, emphasize its ability to modulate cellular ROS levels and target key molecular pathways involved in cancer progression. This study sheds light on the promising therapeutic implications of C. inophyllum extract as a novel agent for cancer treatment, which is safe for normal cells.

Polycaprolactone (PCL), a hydrophobic-degradable polyester, has been widely investigated and extensively developed, to increase the biocompatibility for tissue engineering. This research was the first trial to evaluate the intrinsic biological responses of human Wharton’s Jelly Mesenchymal Stem Cells (hWJMSCs) cultured on alkaline hydrolysis and low-pressure oxygen plasma modified 2D and 3D PCL scaffolds, without adding any differentiation inducers; this has not been reported before. Four types of the substrate were newly established: 2D plasma-treated PCL (2D-TP), 2D non-plasma-treated PCL (2D-NP), 3D plasma-treated PCL (3D-TP), and 3D non-plasma-treated PCL (3D-NP). Physicochemical characterization revealed that only plasma-treated PCL scaffolds significantly increased the hydrophilicity and % oxygen/carbon ratio on the surfaces. The RMS roughness of 3D was higher than 2D conformation, whilst the plasma-treated surfaces were rougher than the non-plasma treated ones. The cytocompatibility test demonstrated that the 2D PCLs enhanced the initial cell attachment in comparison to the 3Ds, indicated by a higher expression of focal adhesion kinase. Meanwhile, the 3Ds promoted cell proliferation and migration as evidence of higher cyclin-A expression and filopodial protrusion, respectively. The 3Ds potentially protected the cell from apoptosis/necrosis but also altered the pluripotency/differentiation-related gene expression. In summary, the different configuration and surface properties of PCL scaffolds displayed the significant potential and effectiveness for facilitating stem cell growth and differentiation in vitro. The cell–substrate interactions on modified surface PCL may provide some information which could be further applied in substrate architecture for stem cell accommodation in cell delivery system for tissue repair.

Cell-based therapies and tissue engineering applications require biocompatible substrates that support and regulate the growth, survival, and differentiation of specific cell types. Extensive research efforts in regenerative medicine are devoted to the development of tunable biomaterials which support various cell types including stem cells. In this research, the non-cytotoxic biopolymer polycaprolactone (PCL) was fabricated into 2D and 3D scaffolds with or without the low-pressure oxygen plasma treatment to enhance hydrophilicity. Cellular responses and biocompatibility were evaluated using a human Wharton’s jelly mesenchymal stem cell line (BCP-K1). The 2D PCL scaffolds enhanced initial cell attachment compared to the 3Ds indicated by a higher expression of focal adhesion kinase (FAK). Whilst, the 3D scaffolds promoted cell proliferation and migration as evidenced by higher cyclin A expression and filopodial protrusion, respectively. The 3D scaffolds potentially protected the cell entering to apoptosis/necrosis program and induced cell differentiation, evaluated by gene expression. Both 2D and 3D PCL appeared to have stronger effects on cell behavior than a control substrate (polystyrene). In summarize, the different configuration and surface properties of PCL scaffolds provide various options for modulation of stem cell behaviors, including attachment, proliferation, survival, and differentiation, when combined with specific growth factors and culture conditions.

Stem cells based tissue engineering requires biocompatible materials, which allow the cells to adhere, expand, and differentiate in a large scale. An ideal biomaterial for clinical application should be free from mammalian products which cause immune reactivities and pathogen infections. We invented a novel biodegradable poly(L‐lactic‐co‐ε‐caprolactone)‐sericin (PLCL‐SC) copolymer membrane which was fabricated by electrospinning. Membranes with concentrations of 2.5 or 5% (w/v) SC exhibited qualified texture characteristics with a noncytotoxic release profile. The hydrophilic properties of the membranes were 35–40% higher than those of a standard PLCL and commercial polystyrene (PS). The improved characteristics of the membranes were due to an addition of new functional amide groups, C=O, N–H, and C–N, onto their surfaces. Degradation of the membranes was controllable, depending on the content proportion of SC. Results of thermogram indicated the superior stability and crystallinity of the membranes. These membranes enhanced human Wharton’s jelly mesenchymal stem cells (hWJMSC) proliferation by increasing cyclin A and also promoted cell adhesion by upregulating focal adhesion kinase (FAK). On the membranes, hWJMSC differentiated into a neuronal lineage with the occurrence of nestin. These data suggest that PLCL‐SC electrospun membrane represents some properties which will be useful for tissue engineering and medical applications.

In this study, for the first time, a biodegradable poly(L-lactide-co-ε-caprolactone), PLC 67:33 copolymer was developed for use as temporary scaffolds in reconstructive nerve surgery. The effect of the surface topology and pore architecture were studied on the biocompatibility for supporting the growth of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) and human neuroblastoma cells (hNBCs) as cell models. Porous PLC membranes were prepared by electrospinning and phase immersion precipitation with particulate leaching and nonporous PLC membranes were prepared by solvent casting. From the results, the porous PLC membranes can support hWJ-MSCs and hNBCs cells better than the nonporous PLC membrane, and the interconnected pore scaffold prepared by electrospinning exhibited a more significant supporting attachment of the cells than the open pore and nonporous membranes. We can consider that these electrospun PLC membranes with 3-D interconnecting fiber networks and a high porosity warrant a potential use as nerve guides in reconstructive nerve surgery.