Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 4 ( 2023-02-20), p. 4198-
    Abstract: For SMA patients with only two SMN2 copies, available therapies might be insufficient to counteract lifelong motor neuron (MN) dysfunction. Therefore, additional SMN-independent compounds, supporting SMN-dependent therapies, might be beneficial. Neurocalcin delta (NCALD) reduction, an SMA protective genetic modifier, ameliorates SMA across species. In a low-dose SMN-ASO-treated severe SMA mouse model, presymptomatic intracerebroventricular (i.c.v.) injection of Ncald-ASO at postnatal day 2 (PND2) significantly ameliorates histological and electrophysiological SMA hallmarks at PND21. However, contrary to SMN-ASOs, Ncald-ASOs show a shorter duration of action limiting a long-term benefit. Here, we investigated the longer-term effect of Ncald-ASOs by additional i.c.v. bolus injection at PND28. Two weeks after injection of 500 µg Ncald-ASO in wild-type mice, NCALD was significantly reduced in the brain and spinal cord and well tolerated. Next, we performed a double-blinded preclinical study combining low-dose SMN-ASO (PND1) with 2× i.c.v. Ncald-ASO or CTRL-ASO (100 µg at PND2, 500 µg at PND28). Ncald-ASO re-injection significantly ameliorated electrophysiological defects and NMJ denervation at 2 months. Moreover, we developed and identified a non-toxic and highly efficient human NCALD-ASO that significantly reduced NCALD in hiPSC-derived MNs. This improved both neuronal activity and growth cone maturation of SMA MNs, emphasizing the additional protective effect of NCALD-ASO treatment.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 16 ( 2021-08-05), p. 3466-
    Abstract: Background: Cardiology divisions reshaped their activities during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to analyze the organization of echocardiographic laboratories and echocardiography practice during the second wave of the COVID-19 pandemic in Italy, and the expectations for the post-COVID era. Methods: We analyzed two different time periods: the month of November during the second wave of the COVID-19 pandemic (2020) and the identical month during 2019 (November 2019). Results: During the second wave of the COVID-19 pandemic, the hospital activity was partially reduced in 42 (60%) and wholly interrupted in 3 (4%) echocardiographic laboratories, whereas outpatient echocardiographic activity was partially reduced in 41 (59%) and completely interrupted in 7 (10%) laboratories. We observed an important change in the organization of activities in the echocardiography laboratory which reduced the operator-risk and improved self-protection of operators by using appropriate personal protection equipment. Operators wore FFP2 in 58 centers (83%) during trans-thoracic echocardiography (TTE), in 65 centers (93%) during transesophageal echocardiography (TEE) and 63 centers (90%) during stress echocardiography. The second wave caused a significant reduction in number of echocardiographic exams, compared to November 2019 (from 513 ± 539 to 341 ± 299 exams per center, −34%, p 〈 0.001). On average, there was a significant increase in the outpatient waiting list for elective echocardiographic exams (from 32.0 ± 28.1 to 45.5 ± 44.9 days, +41%, p 〈 0.001), with a reduction of in-hospital waiting list (2.9 ± 2.4 to 2.4 ± 2.0 days, −17%, p 〈 0.001). We observed a large diffusion of point-of-care cardiac ultrasound (88%), with a significant increase of lung ultrasound usage in 30 centers (43%) during 2019, extended to all centers in 2020. Carbon dioxide production by examination is an indicator of the environmental impact of technology (100-fold less with echocardiography compared to other cardiac imaging techniques). It was ignored in 2019 by 100% of centers, and currently it is considered potentially crucial for decision-making in cardiac imaging by 65 centers (93%). Conclusions: In one year, major changes occurred in echocardiography practice and culture. The examination structure changed with extensive usage of point-of-care cardiac ultrasound and with lung ultrasound embedded by default in the TTE examination, as well as the COVID-19 testing.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Venereology, MDPI AG, Vol. 1, No. 1 ( 2022-01-29), p. 47-80
    Abstract: The multistep translational science behind new drugs comprehends the entire process through laboratory, clinical, and community observations turned into health interventions. The development of new drug options from discovering targets and leading compounds in basic research for implementing therapeutic guidelines contributes to the emergence of health policies essential for infection control. This review updates the translational research in the scenario of the most common non-viral sexually transmitted infection (STI), trichomoniasis. Paradoxically to its high occurrence, it is considered neglected since notification is not mandatory. It turns into a stable disease with health complications, and receives little emphasis from public health programs to control STI. Although related to curable STIs, the current drugs, metronidazole and tinidazole, present therapeutic failures. The need for new options to treat trichomoniasis is established by basic research studies and patents revealing novel synthetic compounds and natural products presenting anti-Trichomonas vaginalis activities, mainly based on in vitro findings. Clinical trials are still focused on new routes of administration for conventional drugs. In addition, nanotechnology approaches are in their infancy, shedding light on potential possibilities for creating more effective, targeted, and safe delivery systems. Overall, the novel proposed approaches need, in addition to pharmaceutical development and efficacy assessments, to ensure that the quality requirements for their use as medicines are met. It is essential to overcome these issues to cross the “Death Valley” of drug discovery and to advance in the translational science criteria in the trichomoniasis drug development field.
    Type of Medium: Online Resource
    ISSN: 2674-0710
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 3136516-4
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Cells, MDPI AG, Vol. 12, No. 15 ( 2023-07-27), p. 1952-
    Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs). Astrocytes display a toxic phenotype in ALS, which results in MN damage. Glutamate (Glu)-mediated excitotoxicity and group I metabotropic glutamate receptors (mGluRs) play a pathological role in the disease progression. We previously demonstrated that in vivo genetic ablation or pharmacological modulation of mGluR5 reduced astrocyte activation and MN death, prolonged survival and ameliorated the clinical progression in the SOD1G93A mouse model of ALS. This study aimed to investigate in vitro the effects of mGluR5 downregulation on the reactive spinal cord astrocytes cultured from adult late symptomatic SOD1G93A mice. We observed that mGluR5 downregulation in SOD1G93A astrocytes diminished the cytosolic Ca2+ overload under resting conditions and after mGluR5 simulation and reduced the expression of the reactive glial markers GFAP, S100β and vimentin. In vitro exposure to an anti-mGluR5 antisense oligonucleotide or to the negative allosteric modulator CTEP also ameliorated the altered reactive astrocyte phenotype. Downregulating mGluR5 in SOD1G93A mice reduced the synthesis and release of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and ameliorated the cellular bioenergetic profile by improving the diminished oxygen consumption and ATP synthesis and by lowering the excessive lactate dehydrogenase activity. Most relevantly, mGluR5 downregulation hampered the neurotoxicity of SOD1G93A astrocytes co-cultured with spinal cord MNs. We conclude that selective reduction in mGluR5 expression in SOD1G93A astrocytes positively modulates the astrocyte reactive phenotype and neurotoxicity towards MNs, further supporting mGluR5 as a promising therapeutic target in ALS.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages