Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells.

BACKGROUND: Eukaryotic cells demonstrate two tightly linked vesicular transport systems, comprising intracellular vesicle transport and extracellular vesicle transport system. Intracellular transport vesicles can translocate biomolecules between compartments inside the cell, for example, proteins from the rough endoplasmic reticulum to the Golgi apparatus. Whereas, the secreted vesicles so-called extracellular vesicles facilitate the transport of biomolecules, for example, nucleic acids, proteins and lipids between cells. Vesicles can be formed during the process of endocytosis or/and autophagy and not only act as mediators of intra- and inter-cellular communication but also represent pathological conditions of cells or tissues. METHODS: In this review, we searched articles in PubMed, published between 2000 and 2020, with following terms: autophagy, autophagocytosis, transport vesicles, lysosomes, endosomes, exocytosis, exosomes, alone or in different combinations. The biological functions that were selected based on relevancy to our topic include cellular homeostasis and tumorigenesis. RESULTS: The searched literature shows that there is a high degree of synergies between exosome biogenesis and autophagy, which encompass endocytosis and endosomes, lysosomes, exocytosis and exosomes, autophagocytosis, autophagosomes and amphisomes. These transport systems not only maintain cellular homeostasis but also operate synergically against fluctuations in the external and internal environment such as during tumorigenesis and metastasis. Additionally, exosomal and autophagic proteins may serve as cancer diagnosis approaches. CONCLUSION: Exosomal and autophagy pathways play pivotal roles in homeostasis and metastasis of tumor cells. Understanding the crosstalk between endomembrane organelles and vesicular trafficking may expand our insight into cooperative functions of exosomal and autophagy pathways during disease progression and may help to develop effective therapies against lysosomal diseases including cancers and beyond.

Free and hydrogel encapsulated exosome-based therapies in regenerative medicine.

Over the last few decades, mesenchymal stem cells-derived exosomes (MSCs-Ex) have attracted a lot of attention as a therapeutic tool in regenerative medicine. Exosomes are extracellular vehicles (EVs) that play important roles in cell-cell communication through various processes such as stress response, senescence, angiogenesis, and cell differentiation. Success in the field of regenerative medicine sparked exploration of the potential use of exosomes as key therapeutic effectors of MSCs to promote tissue regeneration. Various approaches including direct injection, intravenous injection, intraperitoneal injection, oral administration, and hydrogel-based encapsulation have been exploited to deliver exosomes to target tissues in different disease models. Despite significant advances in exosome therapy, it is unclear which approach is more effective for administering exosomes. Herein, we critically review the emerging progress in the applications of exosomes in the form of free or association with hydrogels as therapeutic agents for applications in regenerative medicine.

Polymorphisms in Beta-2 Adrenergic Receptor Gene and Association with Tuberculosis.

PURPOSE: Genetic susceptibility for tuberculosis in human has been previously demonstrated. Polymorphisms in genes involved in immune responses may alter the susceptibility of individuals to tuberculosis. Polymorphisms of beta-2 adrenergic receptor (ADRB2) gene can be possibly an important risk factor in tuberculosis. In this study, the association between rs1042713 (Arg16Gly +46A>G) and rs1042714 (Gln27Glu +79C>G) polymorphisms in ADRB2 gene and tuberculosis was evaluated. METHODS: Genotype distributions of the rs1042713 (Arg16Gly +46A>G) and rs1042714 (Gln27Glu +79C>G) polymorphisms in ADRB2 gene in 106 patients with pulmonary tuberculosis and 88 healthy subjects were studied by PCR-RFLP method in an Iranian population. RESULTS: The frequency of rs1042713*G and rs1042714*G alleles in ADRB2 gene in tuberculosis patients was significantly different from healthy controls [odds ratio (OR) 0.176, 95% confidence interval (CI) 0.065-0.48, P value <0.001 and OR 0.45, 95% CI 0.247-0.825, P value = 0.009, respectively]. There were no significant differences in haplotype analysis between the patients and control subjects. CONCLUSION: The association was reported between rs1042713 and rs1042714 polymorphisms in ADRB2 gene and tuberculosis for the first time. rs1042713*G and rs1042714*G polymorphisms in ADRB2 gene makes people more susceptible to develop the disease.