Abstract. Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects. Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs. Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation. The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling. Human aldehyde dehydrogenase-positive (ALDH + ) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis. Furthermore, the number of mammosphere-forming units (MFUs) in ALDH + breast CSCs and MCF7 cells was determined. It was determined that glucosamine treatment decreased the viability of ALDH + breast CSCs. Glucosamine treatment also decreased the stemness of ALDH + breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs. This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.

A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis despite growing medical advancements. Researchers have been looking for better and more effective treatments targeting the molecular pathways of gliomas due to glioblastomas’ ability to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to maintaining the glioma population, which benefits from its ability to self-renew and differentiate. Recent research has reported that through the introduction of umbilical cord mesenchymal stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be downregulated. It has more currently been found out that UCMSC release extracellular vesicles (EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses literature to discuss all possible miRNAs contained within the UCMSC’s EVs and to elaborate on their molecular mechanisms in halting gliomas and GSC growth. This review will also include the challenges and limitations, to account for which more in vivo research is suggested. In conclusion, this review highlights how miRNAs contained within UCMSC’s EVs are able to downregulate multiple prominent pathways in the survival of gliomas.

Latar belakang: Untuk menganalisis hubungan antara stres oksidatif pada sel glioma manusia dengan derajat keganasan, sehingga dapat mengeksplorasi peranan stress oksidatif sebagai petanda tumor dalam menentukan progresi tumor. Metode: Sampel terdiri dari 21 jaringan tumor dan 5 jaringan otak normal dari penderita glioma. Stres oksidatif dianalisis melalui pengukuran Malondyaldehida (MDA) yang menggambarkan kerusakan lipid dan kadar karbonil untuk kerusakan protein, serta 8-hydroxy-2'-deoxyguanosine/ 8-OHdG untuk kerusakan DNA. Selain itu, dilakukan analisis terhadap ekspresi Manganese Superoxide Dismutase (MnSOD) sebagai enzim antioksidan utama yang berperan dalam stres oksidatif. Ekspresi MnSOD dianalisis melalui pengukuran mRNA MnSOD menggunakan Real Time PCR dan aktivitas spesifik enzim MnSOD menggunakan inhibisi xantin oksidase (kit RanSOD). Derajat keganasan ditentukan berdasarkan pemeriksaan histopatologis. Analisis statistik dengan menggunakan t-test dan uji korelasi Pearson. Hasil: Kadar MDA, karbonil dan 8-OHdG sebagai parameter stres oksidatif pada glioma lebih tinggi bermakna dibandingkan dengan otak normal. Kadar MDA dan karbonil ini meningkat sesuai dengan derajat keganasan. Ekspresi relatif mRNA MnSOD dan aktivitas spesisifik enzim MnSOD pada glioma lebih tinggi bermakna dibandingkan dengan otak normal. Ekspresi relatif mRNA MnSOD tersebut meningkat bermakna sesuai dengan derajat keganasan. Namun, aktivitas spesifik enzim MnSOD pada glioma derajat tinggi lebih rendah bermakna dibandingkan glioma derajat rendah, dengan demikian terdapat ketidak sesuaian antara sintesis mRNA MnSOD dengan aktivitas spesifiknya. Terdapat korelasi positif antara mRNA MnSOD dengan kadar MDA.

ABSTRAK ABSTRACTBackground: Glioblastoma multiforme (GBM) is a primary malignant brain tumor which has poor prognosis. High incidence of oxidative stress-based therapy resistance could be related to the high antioxidant status of GBM cells. Our previous study has reported that manganese superoxide dismutase (MnSOD) antioxidant expression was significantly higher in high grade glioma than in low grade. The aim of this study was to analyze the impact of MnSOD suppression toward GBM cell survival.

Background: Insulin resistance is a condition in which insulin cannot take up glucose, increasing blood glucose. Elderly people are more exposed to insulin resistance, requiring dietary interventions that extend longevity. Trehalose, a naturally occurring sugar, showed potentially reduce insulin resistance which can be measured using the HOMA-IR (Homeostatis Model Assessment-Insulin Resistance) index. Objectives: This study aimed to assess HOMA-IR levels as a parameter of insulin resistance in old rats after giving trehalose sugar. Methods: Experimental research with 28 male Wistar rats (Rattus novergicus) was separated into 4 groups, the control group of young rats (Group A), the control group of old rats (Group B), a group of old rats that were given 2% Trehalose solution (Group C), and a group of old rats that given 2% sucrose solution (Group D) that observed for 8 weeks. Results: The results showed differences in HOMA-IR levels (p<0.001) between old and young subjects. The intervention in Group C was optimal in reducing levels of HOMA-IR (p<0.001) by 18.2% compared with the old control, while Group D increased levels of HOMA-IR by 14.3% (p<0.001) compared with the old control. The age of the subjects with HOMA-IR level is positively correlated (p<0.001; r=0.721) and the weight of subjects with the HOMA-IR level is also positively correlated (p<0.001; r=0.698), indicating that the older and the greater weight of subject resulting in the bigger of HOMA-IR value. Conclusion: Trehalose is effective in reducing HOMA-IR levels as a parameter of insulin resistance in old rats.