Exosomes are the small extracellular vesicles secreted by cells for intercellular communication. Exosomes are rich in therapeutic cargos such as microRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids. Recently, many studies have focused on miRNAs as a promising therapeutic factor to support cartilage regeneration. Exosomes are known to contain a substantial amount of a variety of miRNAs. miRNAs regulate the post-transcriptional gene expression by base-pairing with the target messenger RNA (mRNA), leading to gene silencing. Several exosomal miRNAs have been found to play a role in cartilage regeneration by promoting chondrocyte proliferation and matrix secretion, reducing scar tissue formation, and subsiding inflammation. The exosomal miRNA cargo can be modulated using techniques such as cell transfection and priming as well as post-secretion modifications to upregulate specific miRNAs to enhance the therapeutic effect. Exosomes are delivered to the joints through direct injection or via encapsulation within a scaffold for sustained release. To date, exosome therapy for cartilage injuries has yet to be optimized as the ideal cell source for exosomes, and the dose and method of delivery have yet to be identified. More importantly, a deeper understanding of the role of exosomal miRNAs in cartilage repair is paramount for the development of more effective exosome therapy.

Plant extracts comprise a complex mixture of natural compounds with diverse biological activities including anticancer activities. This has made the use of plant extracts a trending strategy in cancer treatment. In addition, plants’ active constituents such as polyphenols could confer protective effects on normal cells against damage by free radicals as well as lessen the toxicity of chemotherapeutic drugs. Recently, many emerging studies revealed the combinatory uses of plant extracts and individual therapeutic compounds that could be a promising panacea in hampering multiple signaling pathways involved in cancer development and progression. Besides enhancing the therapeutic efficacy, this has also been proven to reduce the dosage of chemotherapeutic drugs used, and hence overcome multiple drug resistance and minimize treatment side effects. Notably, combined use of plant extracts with chemotherapeutics drugs was shown to enhance anticancer effects through modulating various signaling pathways, such as P13K/AKT, NF-κB, JNK, ERK, WNT/β-catenin, and many more. Hence, this review aims to comprehensively summarize both In Vitro and In Vivo mechanisms of actions of well-studied plant extracts, such as Ganoderma Lucidum, Korean red ginseng, Garcinia sp., curcumin, and luteolin extracts in augmenting anticancer properties of the conventional chemotherapeutic drugs from an extensive literature search of recent publications.

Therapeutic failure in cancer often arises from the ability of tumor cells to adapt to external stressors such as drug exposure, metabolic and oxidative stress, and immune surveillance within the tumor microenvironment (TME). This adaptive capacity is a significant factor contributing to poor clinical outcomes and the lethality associated with many aggressive cancer types. During tumor progression, a subpopulation of cells may acquire stem-like characteristics, leading to the development of cancer stem cells (CSCs), which play a pivotal role in resistance and disease recurrence. A key driver of this process is epigenetic reprogramming, which alters histone modifications and chromatin architecture in response to environmental stimuli. These modifications activate genes associated with stemness by creating transcriptionally permissive chromatin regions, while simultaneously silencing genes involved in differentiation, thereby maintaining the tumor cells’ undifferentiated state. This cellular plasticity enables cancer cells to undergo transdifferentiation or dedifferentiation, enhancing their capacity for survival and adaptation. Importantly, distinct transcriptional states are often regulated by specific epigenetic signatures, some of which are valuable for tumor subtype classification, prognosis assessment, and treatment response prediction. Furthermore, certain epigenetic biomarkers show considerable promise for detecting tumor recurrence and monitoring minimal residual disease with high sensitivity. In this review, we examine how epigenetic reprogramming influences chromatin plasticity to promote stemness and therapeutic resistance. Additionally, we discuss ongoing translational research aimed at leveraging these mechanisms to advance precision oncology, with the ultimate goal of improving diagnostic accuracy and therapeutic efficacy.