Therapeutic effects and perspective of stem cell extracellular vesicles in aging and cancer.

Senescent cells can secrete a plethora of cytokines which induce senescent phenotype of neighboring cells and was called senescence-associated secretory phenotype. Previously, it was believed that cancer was caused by the infinite division and uncontrolled proliferation of cells. Based on this, anticancer treatments were all aimed at killing cancer cells. Cancer is now considered an age-related disease. Cancer cells are not exogenous, but one of the worst results of injuries which initially induce cell senescence. Therefore, reversing cell senescence can fundamentally prevent and treat cancer. Though current anticancer treatments induce the cancer cells apoptosis, they induce senescence of normal cells at the same time, thus promoting the occurrence and development of cancer and forming a vicious circle. Extracellular vesicles (EVs) are nano-sized vesicles which partially mirror their parent cells. In the tumor microenvironment, EVs of senescent cells can change the expression profile of cancer cells, contributing to their resistance to chemotherapy. There is growing evidence indicates that stem cell EVs exert effective antiaging and anticancer actions by transferring functional microRNAs and proteins. This review will summarize the therapeutic role of stem cell EVs in reversing aging and cancer, which suggests the broad clinical application perspective.

Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours.

The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti-tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti-tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME-such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell-based microenvironment therapies-to provide novel ideas for producing breakthroughs in tumour therapy strategies.

Lipid layer thickness and tear meniscus height measurements for the differential diagnosis of evaporative dry eye subtypes.

AIM: To explore a new diagnostic index for differentiating the evaporative dry eye (EDE) subtypes by analysis of their respective clinical characteristics. METHODS: A cross-sectional study of 139 patients (139 eyes) with EDE who were enrolled and classified as obstructive meibomian gland dysfunction (MGD) (n=81) and non-obstructive MGD (n=58) EDE. All patients completed a Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and were evaluated for average lipid layer thickness (LLT), tear meniscus height measurements (TMH), tear break-up time (TBUT), ocular surface staining score, Schirmer I test (SIT), lid margin abnormalities, and meibomian gland function and morphology. RESULTS: Age, average LLT, TMH, scores of lid margin abnormalities, meibum quality, meibomian gland loss (MGL) (all P≤0.001), and TBUT (P=0.03) were all significantly different between obstructive MGD EDE patients and non-obstructive MGD EDE patients. Average LLT in obstructive MGD EDE was correlated with meibomian expressibility (r=-0.541, P≤0.001), lid margin abnormalities were marginally not significant (r=0.197, P=0.077), and TMH was correlated with MGL (total MGL: r=0.552, P≤0.001; upper MGL: r=0.438, P≤0.001; lower MGL: r=0.407, P≤0.001). Average LLT in non-obstructive MGD EDE, was correlated with meibomian expressibility and Oxford staining (r=-0.396, P=0.002; r=-0.461, P≤0.001). The efficiency of combining average LLT and TMH was optimal, with a sensitivity of 80.2% and a specificity of 74.1%. Obstructive MGD EDE patients had an average LLT≥69 nm and TMH≥0.25 mm, while non-obstructive MGD EDE patients had an average LLT<69 nm and TMH<0.25 mm. CONCLUSION: Obstructive MGD EDE and non-obstructive MGD EDE have significantly different clinical characteristics. Combining average LLT and TMH measurements enhanced their reliability for differentiating these two subtypes and provided guidance for offering more precise treatments for EDE subtypes.