Science & Nature reviews, August 2021 (2)

These are ChemDiv's reviews on Nature and Science Journal articles. It is the second part of the August reviews. Today we emphasize Drug research, Immunology, Physiology, and Genetic Engineering.

Drug research

Tsiantoulas, D., Eslami, M., Obermayer, G. et al. APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans. Nature 597, 92–96 (2021)

A new study in the pages of Nature reveals the role of a proliferation-inducing ligand (APRIL) in atherosclerosis remains. It is known that atherosclerosis is a disease in which the wall of the artery develops abnormalities, called lesions. Unfortunately, this disease causes heart attacks and strokes, which are the leading causes of mortality worldwide. For this reason, the study of the pathophysiological properties of the key molecules (for example, APRIL) and the search for treatment are of paramount importance. Here scientists show that ablation or depletion of APRIL aggravates atherosclerosis in mice. Indeed, treatment with a specific anti-APRIL antibody reduced experimental atherosclerosis, which may be a new treatment strategy.

Physiology

Ambrosi, T.H., Marecic, O., McArdle, A. et al. Aged skeletal stem cells generate an inflammatory degenerative niche. Nature 597, 256–262 (2021)

The next important research in Nature concerns aging of the body especially changes in skeletal tissue composition and osteoporosis. Sooner or later, we start to worry about such a medical challenge as the aging body. Our organisms contain stem cells that consistently give rise to new cells for tissue building and regeneration. Nevertheless, we are unable to escape aging. The reason is that regenerative stem cells and their supportive niche environment deteriorate with age. Scientists show that intrinsic aging of skeletal stem cells in mice skews the differentiation of bone and blood lineages, leading to fragile bones that regenerate poorly. This analysis provides mechanistic insights into the complex, multifactorial mechanisms that underlie aging and offer prospects for rejuvenating the aged skeletal system.

Immunology

Amir, M., Zeng, M. Y. Immune imprinting in utero. Science 373, 6558, 967-968 (2021)

It is known that one of the fundamental properties of the immune system is its ability to develop the memory of previous encounters, which leads to enhanced responsiveness to subsequent challenges. So, what about immune systems development in utero? Mild maternal infections are often self-resolved and underdiagnosed, and it remains poorly understood whether transient maternal inflammation leaves an immunologic scar in offspring. On the page of Science's issue researchers show that a transient, mild infection encountered during prenatal development can alter the threshold of activation and enhanced resistance to infection. Although some side effects of this phenomenon can be co-opted to develop optimal immune fitness in the future.

Genetic Engineering

Segel, M., Lash, B., Song, G. et al. Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery. Science 373, 6557, 882-889 (2021)

The mammalian genome contains a huge number of genetic sequences that were integrated throughout evolution by retroviruses and retroelements. Some of them are useless for the cell, many pose a threat to the integrity of the genome. It’s still not clear why the organism maintains these "genetic cohabitants". However, on the pages of Science researchers show the third group of «foreign» sequences, which contain retroviral-like protein PEG10. This group has been retooled by mammalian cells to perform essential roles in development. The peculiarity of protein PEG10 is that it directly binds to and secretes its own mRNA in extracellular virus-like capsids. Then scientists construct PEG10 to package, secrete, and deliver specific RNAs and demonstrate that it’s an efficient therapeutic delivery modality.

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