Intranasal delivery of mesenchymal stem cell secretome repairs the brain of Alzheimer’s mice

The multiplicity of systems affected in Alzheimer’s disease (AD) brains calls for multi-target therapies. Although mesenchymal stem cells (MSC) are promising candidates, their clinical application is limited because of risks related to their direct implantation in the host. This could be overcome by exploiting their paracrine action. We herein demonstrate that in vivo systemic administration of secretome collected from MSC exposed in vitro to AD mouse brain homogenates (MSC-CS), fully replicates the cell-mediated neuroreparative effects in APP/PS1 AD mice. We found a complete but transient memory recovery by 7 days, which vanished by 14 days, after a single MSC-CS intravenous administration in 12-month or 22–24-month-old mice. Treatment significantly reduced plaque load, microglia activation, and expression of cytokines in astrocytes in younger, but not aged, mice at 7 days. To optimize efficacy, we established a sustained treatment protocol in aged mice through intranasal route. Once-weekly intranasal administration of MSC-CS induced persistent memory recovery, with dramatic reduction of plaques surrounded by a lower density of β-amyloid oligomers. Gliosis and the phagocytic marker CD68 were decreased. We found a higher neuronal density in cortex and hippocampus, associated with a reduction in hippocampal shrinkage and a longer lifespan indicating healthier conditions of MSC-CS-treated compared to vehicle-treated APP/PS1 mice. Our data prove that MSC-CS displays a great multi-level therapeutic potential, and lay the foundation for identifying the therapeutic secretome bioreactors leading to the development of an efficacious multi-reparative cocktail drug, towards abrogating the need for MSC implantation and risks related to their direct use.Subject terms: Neural ageing, Neurological disorders, Inflammation     

Changes in receptor status after treatment with tamoxifen in endometrial cancer

Estrogen (ER) and progesterone receptor (PgR) status was determined in 41 women with operable endometrial cancer before and after administration of tamoxifen (TAM). The first sample was obtained by hysteroscopy to ensure a precise biopsy of neoplastic tissue; the second was done on the surgical specimen. PgR content was significantly increased after TAM treatment and this data was compared with the degree of tumor differentiation.     

Leveraging substrate flexibility and product selectivity of acetogens in two-stage systems for chemical production

Carbon dioxide (CO₂) stands out as sustainable feedstock for developing a circular carbon economy whose energy supply could be obtained by boosting the production of clean hydrogen from renewable electricity. H₂-dependent CO₂ gas fermentation using acetogenic microorganisms offers a viable solution of increasingly demonstrated value. While gas fermentation advances to achieve commercial process scalability, which is currently limited to a few products such as acetate and ethanol, it is worth taking the best of the current state-of-the-art technology by its integration within innovative bioconversion schemes. This review presents multiple scenarios where gas fermentation by acetogens integrate into double-stage biotechnological production processes that use CO₂ as sole carbon feedstock and H₂ as energy carrier for products' synthesis. In the integration schemes here reviewed, the first stage can be biotic or abiotic while the second stage is biotic. When the first stage is biotic, acetogens act as a biological platform to generate chemical intermediates such as acetate, formate and ethanol that become substrates for a second fermentation stage. This approach holds the potential to enhance process titre/rate/yield metrics and products' spectrum. Alternatively, when the first stage is abiotic, the integrated two-stage scheme foresees, in the first stage, the catalytic transformation of CO₂ into C₁ products that, in the second stage, can be metabolized by acetogens. This latter scheme leverages the metabolic flexibility of acetogens in efficient utilization of the products of CO₂ abiotic hydrogenation, namely formate and methanol, to synthesize multicarbon compounds but also to act as flexible catalysts for hydrogen storage or production.     

Characteristics of the influenza type A (H3N2) epidemic in Omsk in January 1985

The work presents the data obtained in analysis of the epidemic situation among the population of Omsk in January-February 1985 and the characterization of the isolated strains of influenza A (H3N2) virus, determines the specific features of the course of the influenza epidemic process among different social and age groups, evaluates anti-influenza measures.