Cancer stem cell-derived exosomes in CD8+ T cell exhaustion.

Tumor-derived extracellular vesicles (EVs) are one of the most important ways of intercellular communication and signaling. Cancer stem cells (CSCs) secrete EVs to modulate immune checkpoint molecules and evade immune surveillance. Activated CD8+ T cells known as cytotoxic T lymphocytes (CTLs) are the most powerful anti-cancer adaptive cells. Their activity is compromised upon encountering cells and signaling within the tumor microenvironment (TME), resulting in hyporesponsiveness called exhaustion. CSC-derived exosomes express programmed death ligand-1 (PD-L1) and upregulate programmed death-1 (PD-1) on CD8+ T cells to promote their exhaustion. PD-L1 expression on tumor-derived exosomes appears to be induced by CSC-derived exosomes containing transforming growth factor (TGF)-ß. Tenascin-C is another constituent of CSC exosomes that acts on mammalian target of rapamycin (mTOR) signaling in T cells. Glycolysis is a metabolic event promoted by the inducing effect of CSC-derived exosomes on hypoxia-inducible factor-1α (HIF-1α). CSC interaction with CD8+ T cells is even more complex as the CSC-derived exosomes contain Notch1 to stimulate stemness in non-tumor cells, and the inducible effect of Notch1 on PD-1 promotes CD8+ T cell exhaustion. CSC exosome targeting has not been extensively studied yet. Advances in the field will open up new therapeutic windows and shape the future of cancer immunotherapy.

Normal reference values for Tc-99m pertechnetate thyroid uptake in northern Iranian population: A single-center experience.

Background: The normal reference values for the thyroid uptake of radioactive iodine and Tc-99m pertechnetate in euthyroid patients vary by geographical location as well as the amount of iodine intake in the diet. The present study examines the normal reference values for thyroid uptake of Tc-99m pertechnetate in the North of Iran. Methods: The participants of this study were 64 patients (all over 20 years of age) who had referred to the Nuclear Medicine Center of the Shahid Beheshti Hospital for thyroid scan over the period between March 2018 and May 2020. It is worth mentioning that relying on laboratory test results, only patients with normal thyroid function were included in this cross-sectional study. Results: The median, the 5th and 95th percentiles and thyroid uptake range of 99mTc-pertechnetate in euthyroid patients were 0.9, 0.6 to 1.8% and 0.54 - 1.80%, respectively. Conclusion: The percentage of uptake in the thyroid gland in each geographical area varies based on race and diet content, so it is necessary to determine the percentage of uptake in each specific region and even check it periodically.

Hydrogel Encapsulation Techniques and Its Clinical Applications in Drug Delivery and Regenerative Medicine: A Systematic Review.

Hydrogel encapsulation is a promising carrier for cell and drug delivery due to its ability to protect the encapsulated entities from harsh physiological conditions and enhance their therapeutic efficacy and bioavailability. However, there is not yet consensus on the optimal hydrogel type, encapsulation method, and clinical application. Therefore, a systematic review of hydrogel encapsulation techniques and their potential for clinical application is needed to provide a comprehensive and up-to-date overview. In this systematic review, we searched electronic databases for articles published between 2008 and 2023 that described the encapsulation of cells or drug molecules within hydrogels. Herein, we identified 9 relevant studies that met the inclusion and exclusion criteria of our study. Our analysis revealed that the physicochemical properties of the hydrogel, such as its porosity, swelling behavior, and degradation rate, play a critical role in the encapsulation of cells or drug molecules. Furthermore, the encapsulation method, including physical, chemical, or biological methods, can affect the encapsulated entities' stability, bioavailability, and therapeutic efficacy. Challenges of hydrogel encapsulation include poor control over the release of encapsulated entities, limited shelf life, and potential immune responses. Future directions of hydrogel encapsulation include the development of novel hydrogel and encapsulation methods and the integration of hydrogel encapsulation with other technologies, such as 3D printing and gene editing. In conclusion, this review is useful for researchers, clinicians, and policymakers who are interested in this field of drug delivery and regenerative medicine that can serve as a guide for the future development of novel technologies that can be applied into clinical practice.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal- based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.