ABSTRACT
The involvement of cellular senescence in the initiation and propagation of diseases is clearly characterized, making the elimination of senescent cells essential to treat age-related diseases. The development of senolytic drugs demonstrated that targeting these cells limits the deterioration of patients' condition, by inducing apoptosis. Nevertheless, the first generations of senolytics which has been developed displayed their activities through specific mechanisms and demonstrated several limitations during clinical development. However, the rational to eliminate senescent cells remains evident, with the necessity to develop specific therapies in a context of diseases and tissues. The evolutions in the field of drug discovery open the way to a new generation of senolytic therapies, such as immunological approaches (CAR-T cells, Antibody-Drug Conjugated or vaccines), which require preliminary steps of research to identify markers specifically expressed on senescent cells, demonstrating promising specific effects. Currently, the preclinical development of these strategies appears more challenging to avoid strong side effects, but the expected results are commensurate with patients' hopes for treatments. In this review, we highlight the fact that the classical senolytic approach based on drug repurposing display limited efficacy and probably reached its limits in term of clinical development. The recent development of more complex therapies and the extension of interest in the domain of senescence in different fields of research allow to extend the possibility to discover powerful therapies. The future of age-related diseases treatment is linked to the development of new approaches based on cell therapy or immunotherapy to offer the best treatment for patients.
ABSTRACT
One of the main limitations to the application of clusters on applied areas is the limited production; therefore, it is of great interest to up scale cluster production while keeping good size control. The Matrix-Assembly Cluster Source is a new high flux cluster source, which exploits cluster formation inside a solid rare gas matrix that is sputtered by an ion beam. Clusters are formed and ejected in this process. Here we report the production of Ag clusters when the rare gas is replaced by CO2 for the matrix formation at 20 K. Size distributions were determined from scanning transmission electron microscopy analysis of samples with four different metal loadings, 4%, 8%, 14%, and 23% of Ag atoms to CO2 molecules, and two ion beam energies, 1 keV and 2 keV. Cluster mean size showed weak dependence on metal loading, being ≈80 atoms for the first three concentrations, whereas the change in ion beam energy has caused cluster mean size to shift from 86 to 160 atoms. The results are interpreted in terms of bonding energy between Ag and CO2 and compared to the rare gas (Ar) matrix.
ABSTRACT
A multicenter study has been done in France in order to assess the presence of C. trachomatis in the newborn and the young infant. The results show that 4.3% of the infants less than 2 month old are positive. This put forward the question of the screening of pregnant women.
Subject(s)
Carrier State/epidemiology , Chlamydia trachomatis/isolation & purification , Conjunctiva/microbiology , Infant, Premature, Diseases/epidemiology , Trachoma/epidemiology , Female , France/epidemiology , Humans , Infant , Infant, Newborn , Male , PrevalenceABSTRACT
Transurethral prostatectomy and herniorrhaphy were performed as a combined procedure for 63 patients during the period 1974 to 1978. The intraoperative and postoperative courses are compared with those of a control group of 82 patients who underwent herniorrhapies as an isolated procedure during the same period. The simultaneous performance of transurethral prostatectomy and herniorrhaphy in this group of patients was safe as well as cost-effective.
