Formulation of Anti-Oral Mouthwash Nanoemulsion Biofilm Based on Propolis Extract Heterotrigona itama, Tetragonula sapiens, and Tetragonula clypearis

The use of mouthwash is one of the actions against biofilms that are often used. However, commercial mouthwashes have a fairly high alcohol content, which is around 26.9% of the total volume, which is considered to have a prolonged impact where high alcohol content in direct contact with the oral mucosa can cause lesions or abnormalities, resulting in a shift in the medical paradigm towards eco-friendly widely considered as a solution. Propolis with antibacterial ability was formulated using the nanoemulsion steps, which were initiated by separating pure propolis through drying, and then there were variations in the formulation of 3 types of bee propolis: Heterotrigona itama, Tetragonula sapiens, and Tetragonula clypearis along with the addition of Tween 80, propylene glycol, glycerin and then the effect on microbial growth of S. mutans was compared with antimicrobial agents in Brazilian propolis with the identification and comparison of the antibacterial activity stability of the organoleptic formula. Where the active ingredient content of propolis is the highest in H. itama propolis with a total flavonoid content of 38.94 mgQE/L sample and T. clypearis propolis has the lowest total flavonoid content of 14.23 mgQE/L sample with its function as an anti-oral biofilm agent by inhibiting the glucosyltransferase was proven with a minimum percentage of 49% inhibition of S. mutans and degradation of 18% with the use of a combined surfactant proved to be able to increase the stability of the preparation shown at 2:1 (v/v)

The synthesis of amino-functionalized carbon quantum dots-decorated hydroxyapatite as drug delivery agent

Hydroxyapatite (HAp) was combined with amino-functionalized carbon quantum dots (CQDs) to enhance the optical and surface area properties of HAp. The loading of amino-functionalized CQDs could enhance the luminescence of HAp and its UV–Vis absorbance. Additionally, surface area of HAp could be increased from 84.16 to 129.94 m$^{2}$/g by loading amino-functionalized CQDs. The drug release experiment was conducted using acetaminophen. The release happened slowly for amino-functionalized CQDs/HAp, with full release of acetaminophen being observed after 24 h. The enhanced luminescence composite shows high potential for the composite to be used for the controlled release of drugs

The synthesis of amino-functionalized carbon quantum dots-decorated hydroxyapatite as drug delivery agent

Hydroxyapatite (HAp) was combined with amino-functionalized carbon quantum dots (CQDs) to enhance the optical and surface area properties of HAp. The loading of amino-functionalized CQDs could enhance the luminescence of HAp and its UV–Vis absorbance. Additionally, surface area of HAp could be increased from 84.16 to 129.94 m$^{2}$/g by loading amino-functionalized CQDs. The drug release experiment was conducted using acetaminophen. The release happened slowly for amino-functionalized CQDs/HAp, with full release of acetaminophen being observed after 24 h. The enhanced luminescence composite shows high potential for the composite to be used for the controlled release of drugs

Molecular Docking of South Sulawesi Propolis against Fructose 1,6-Bisphosphatase as a Type 2 Diabetes Mellitus Drug

Diabetes mellitus is one of the metabolic diseases, characterized by hyperglycemia, which is usually caused by endogenous glucose production through gluconeogenesis. Furthermore, fructose 1,6-bisphosphatase (FBPase), which is the last enzyme involved in gluconeogenesis, is used as inhibition target due to its relatively safe effect. In addition, It is known that propolis has shown antidiabetic activity through some sets of mechanisms due to its varied constituents. Therefore, this study aims to explore the antidiabetic activity of South Sulawesi propolis compounds against the allosteric site of FBPase (PDB ID: 3KC1) through molecular docking on Autodock Vina. The results show that 18 out of 30 propolis compounds outweigh AMP affinity. Furthermore, only two flavonoids showed 100% interaction similarity to the re-docked native ligand and AMP natural inhibition. These two compounds were Broussoflavonol F and Glyasperin A, which had docking score of -9 kcal/mol and -8.2 kcal/mol, respectively. This indicates that both compounds are capable of being used as FBPase inhibitors for the treatment of diabetes mellitus

A novel model of liver cancer stem cells developed from induced pluripotent stem cells

Background Liver cancer is the second most common cause of cancer-related death. Every type of tumours including liver cancer contains cancer stem cells (CSCs). To date, the molecular mechanism regulating the development of liver CSCs remains unknown. Methods In this study, we tried to generate a new model of liver CSCs by converting mouse induced pluripotent stem cells (miPSCs) with hepatocellular carcinoma (HCC) cell line Huh7 cells conditioned medium (CM). miPSCs treated with CM were injected into the liver of BALB/c nude mice. The developed tumours were then excised and analysed. Results The primary cultured cells from the malignant tumour possessed self-renewal capacity, differentiation potential and tumorigenicity in vivo, which were found rich in liver cancer-associated markers as well as CSC markers. Conclusions We established a model of liver CSCs converting from miPS and showed different stages of stemness during conversion process. Our CSC model will be important to assess the molecular mechanisms necessary to develop liver CSCs and could help in defeating liver cancer

Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15⁻20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies

Signaling Inhibitors Accelerate the Conversion of mouse iPS Cells into Cancer Stem Cells in the Tumor Microenvironment

Cancer stem cells (CSCs) are a class of cancer cells characterized by self-renewal, differentiation and tumorigenic potential. We previously established a model of CSCs by culturing mouse induced pluripotent stem cells (miPSCs) for four weeks in the presence of a conditioned medium (CM) of cancer cell lines, which functioned as the tumor microenvironment. Based on this methodology of developing CSCs from miPSCs, we assessed the risk of 110 non-mutagenic chemical compounds, most of which are known as inhibitors of cytoplasmic signaling pathways, as potential carcinogens. We treated miPSCs with each compound for one week in the presence of a CM of Lewis lung carcinoma (LLC) cells. However, one-week period was too short for the CM to convert miPSCs into CSCs. Consequently, PDO325901 (MEK inhibitor), CHIR99021 (GSK-3 beta inhibitor) and Dasatinib (Abl, Src and c-Kit inhibitor) were found to confer miPSCs with the CSC phenotype in one week. The tumor cells that survived exhibited stemness markers, spheroid formation and tumorigenesis in Balb/c nude mice. Hence, we concluded that the three signal inhibitors accelerated the conversion of miPSCs into CSCs. Similarly to our previous study, we found that the PI3K-Akt signaling pathway was upregulated in the CSCs. Herein, we focused on the expression of relative genes after the treatment with these three inhibitors. Our results demonstrated an increased expression of pik3ca, pik3cb, pik3r5 and pik3r1 genes indicating class IA PI3K as the responsible signaling pathway. Hence, AKT phosphorylation was found to be up-regulated in the obtained CSCs. Inhibition of Erk1/2, tyrosine kinase, and/or GSK-3 beta was implied to be involved in the enhancement of the PI3K-AKT signaling pathway in the undifferentiated cells, resulting in the sustained stemness, and subsequent conversion of miPSCs into CSCs in the tumor microenvironment