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Background: Curcumin is a polyphenol compound with many therapeutic effects. Despite the anti -tumor, antioxidant and anti - inflammatory properties of this pigment, due to poor solubility and instability in the aqueous environments and physiological conditions of the body, its application in the treatment of diseases has been limited. Today researchers are trying to design an efficient nanocarrier for employing this pigment in pharmaceutical applications. Exosomes are lipid nanovesicles are released into the extracellular environment by all types of cells and are responsible for the transfer of biological materials between cells, so they are considered the best candidate for this goal. In this study, we aimed to load curcumin into the exosomes to increase its solubility and stability and facilitate its delivery into ovarian cancer cells. Methods: After isolating the exosome by ultracentrifugation and verifying its structure with SEM, TEM and DLS, curcumin was loaded into the exosome by three methods of incubation, sonication and freeze-thaw cycles. Then, using MTT assay, the toxicity effect of curcumin on SKOV3 cells was investigated. Results: The results showed that the amount of curcumin loading into exosome was very low (less than 10%) and it was found that sonication and freeze-thaw cycles have no effect on increasing the loading of curcumin into the exosome. Based on the results of the toxicity test, IC50 value of free curcumin and exosome-loaded curcumin was 150 µg/ml and 200 µg/ml, respectively. Although the loading percentage of curcumin in the exosome was very low, the MTT results showed that the loading of curcumin in the exosome plays a significant role in its efficient delivery to SKOV3 cells. Conclusions: It can be concluded that despite the very high stability of exosomes and the safety of these cellular nanovesicles, for better efficiency in drug delivery, more studies should be done for optimizing the methods of drug loading into exosomes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is recognized as one of the most common gastrointestinal malignancies across the globe. Despite significant progress in designing novel treatments for CRC, there is a pressing need for more effective therapeutic approaches. Unfortunately, many patients undergoing chemotherapy develop drug resistance, posing a significant challenge for cancer treatment. Non‐coding RNAs (ncRNAs) have been found to play crucial roles in CRC development and its response to chemotherapy. However, there are still gaps in our understanding of interactions among various ncRNAs, such as long non‐coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). These ncRNAs can act as either oncogenes or tumour suppressors, affecting numerous biological functions in different cancers including CRC. A class of ncRNA molecules known as competitive endogenous RNAs (ceRNAs) has emerged as a key player in various cellular processes. These molecules form networks through lncRNA/miRNA/mRNA and circRNA/miRNA/mRNA interactions. In CRC, dysregulation of ceRNA networks has been observed across various cellular processes, including proliferation, apoptosis and angiogenesis. These dysregulations are believed to play a significant role in the progression of CRC and, in certain instances, may contribute to the development of chemoresistance. Enriching our knowledge of these dysregulations holds promise for advancing the field of diagnostic and therapeutic modalities for CRC. In this review, we discuss lncRNA‐ and circRNA‐associated ceRNA networks implicated in the emergence and advancement of drug resistance in colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Given that tumor cells primarily instigate systemic changes through exosome secretion, our study delved into the role of colorectal cancer (CRC)-secreted exosomal miR-224 in stromal reprogramming and its impact on endothelial cell angiogenesis. Furthermore, we assessed the potential clinical significance of a specific signature of circulating serum-derived miRNAs, serving as a non-invasive biomarker for CRC diagnosis. Circulating serum-derived miR-103a-3p, miR-135b-5p, miR-182-5p, and miR-224-5p were significantly up-regulated, while miR-215-5p, and miR-455-5p showed a significant down-regulation in CRC patients than in healthy individuals. Our findings indicated that the expressions of CAF-specific markers (a-SMA and FAP) and CAF-derived cytokines (IL-6, and SDF-1) were induced in fibroblasts stimulated with SW480 CRC exosomes, partly due to Akt activation. As a plausible mechanism, exosomal transfer of miR-224 from SW40 CRC cells may activate stromal fibroblasts, which in turn, may promote endothelial cell sprouting. The study identified PHLPP1 and PHLPP2 as direct targets of miR-224 and demonstrated that CRC-secreted exosomal miR-224 activates Akt signaling by regulating PHLPP1/2 in activated fibroblasts, thereby affecting the stromal cell proliferation and migration. This study established a panel of six-circulating serum-derived miRNAs as a non-invasive biomarker for CRC diagnosis. Also, we proposed a supporting model in which CRC-secreted exosomal miR-224 takes part in the stromal reprogramming to CAFs partly through regulating Akt signaling. This may affect the malignant biological behavior of activated stromal cells and thereby elicit a vascular response within the microenvironment of CRC cells. [ABSTRACT FROM AUTHOR]

Background: Megakaryopoiesis is characterized by progressive polyploidization and the expression of megakaryocytic markers. Numerous transcription factors and physiological signaling pathways regulate this phenomenon. Megakaryocyte differentiation induction in the K562 cell line and hematopoietic stem cells via nanocurcumin drug has been identified in our previous study. K562 cells are typical Chronic Myelogenous Leukemia (CML) cells that are resistant to apoptosis and express the bcr-abl fusion gene. These cells have the potential to differentiate into erythrocytes and megakaryocytes. Curcumin is well known as a component with strong potential to alter NFκB activity in various cells. NFκB pathway regulates various genes such as apoptotic and immune response genes. The aim of the current study is to evaluate the possible role of nanocurcumin in NFκB pathway regulation during the megakaryopoiesis process in the K562 cell line. Materials and Methods: Megakaryocyte markers expression and phenotype alteration of nanocurcumintreated K562 cells have been detected by flow cytometry and microscopy imaging. The nuclear level of the RelA (p65) subunit of NFκB was determined by western blot test in K562 cells during megakaryopoiesis induction via nanocurcumin treatment at different times. The expression of NFκB target genes including c-MYC, BAX, and NQO1 was also analyzed in nanocurcumin-treated K562 cells by quantitative RT-PCR assay at different times. Results: It was demonstrated that nanocurcumin leads to an increase in NFκB activity transiently during megakaryocyte differentiation, which is followed by a change in the expression of c-MYC, BAX, and NQO1 target genes. Conclusion: The NFκB pathway can be considered a new pathway for inducing megakaryocyte differentiation by nanocurcumin for the purposes of in vitro and in vivo megakaryopoiesis experiments. [ABSTRACT FROM AUTHOR]