At the time of writing this commentary (February 2020), the coronavirus COVID‐19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. ...Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS‐CoV‐2 virus may take many months. Moreover, vaccines based on viral‐encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS‐CoV‐2 virus infections. This idea is based on observations that the angiotensin‐converting enzyme 2 (ACE2) very likely serves as the binding site for SARS‐CoV‐2, the strain implicated in the current COVID‐19 epidemic, similarly to strain SARS‐CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS‐CoV‐2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.
MicroRNAs (miRNAs) are short, noncoding RNAs functioning as regulators of the
transcription of protein-coding genes in eukaryotes. During the last two decades,
studies on miRNAs indicate that they ...have potential as diagnostic and prognostic
biomarkers for a wide range of cancers. Research interest in miRNAs has moved to
embrace further medical disciplines, including neuropsychiatric disorders, comparing
miRNA expression and mRNA targets between patient and control blood samples and
postmortem brain tissues, as well as in animal models of neuropsychiatric disorders.
This manuscript reviews recent findings on miRNAs implicated in the pathology of mood
disorders, schizophrenia, and autism, as well as their diagnostic potential, and
their potential as tentative targets for future therapeutics. The plausible
contribution of X chromosome miRNAs to the larger prevalence of major depression
among women is also evaluated.
...the school principals‘ access to such lists was blocked (in advance of any High Court ruling on this matter). Coercion to get vaccinated may reduce public trust in vaccination drives, a crucial ...aspect for combatting the pandemic 8–9. ...while the Israeli vaccination drive demonstrated high real-world efficacy against COVID-19 1,2, the efficacy of the BNT162b2 and other approved COVID-19 vaccines against future SARS-CoV-2 variants remain uncertain. ...developed countries in a similar COVID-19 situation to that of Israel, where its spread has been contained following vaccination of over half their population, are urged to donate their surplus vaccines to the World Health Organization COVAX initiative, so that they may benefit the populations in developing countries 10,11.
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulinlike growth factor 1 (IGF1) deficiencies. Life-long exposure to minute ...endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered. Recent genomic analyses identified a series of metabolic genes that are overrepresented in patients with LS. Given the augmented expression of these genes in a low IGF1 milieu, we hypothesized that they may constitute targets for IGF1 action. Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular redox control by thioredoxin. TXNIP serves as a glucose and oxidative stress sensor, being commonly silenced by genetic or epigenetic events in cancer cells. Consistent with its enhanced expression in LS, we provide evidence that TXNIP gene expression is negatively regulated by IGF1. These results were corroborated in animal studies. In addition, we show that oxidative and glucose stresses led to marked increases in TXNIP expression. Supplementation of IGF1 attenuated TXNIP levels, suggesting that IGF1 exerts its antiapoptotic effect via inhibition of TXNIP. Augmented TXNIP expression in LS may account for cancer protection in this condition. Finally, TXNIP levels could be potentially useful in the clinic as a predictive or diagnostic biomarker for IGF1R-targeted therapies.
Since its outbreak in late 2019, the SARS‐Cov‐2 pandemic already infected over 3.7 million people and claimed more than 250,000 lives globally. At least 1 year may take for an approved vaccine to be ...in place, and meanwhile millions more could be infected, some with fatal outcome. Over thousand clinical trials with COVID‐19 patients are already listed in ClinicalTrials.com, some of them for assessing the utility of therapeutics approved for other conditions. However, clinical trials take many months, and are typically done with small cohorts. A much faster and by far more efficient method for rapidly identifying approved therapeutics that can be repurposed for treating COVID‐19 patients is data mining their past and current electronic health and prescription records for identifying drugs that may protect infected individuals from severe COVID‐19 symptoms. Examples are discussed for applying health and prescription records for assessing the potential repurposing (repositioning) of angiotensin receptor blockers, estradiol, or antiandrogens for reducing COVID‐19 morbidity and fatalities. Data mining of prescription records of COVID‐19 patients will not cancel the need for conducting controlled clinical trials, but could substantially assist in trial design, drug choice, inclusion and exclusion criteria, and prioritization. This approach requires a strong commitment of health provides for open collaboration with the biomedical research community, as health provides are typically the sole owners of retrospective drug prescription records.
Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind ...the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.
•Oxytocin combined with citalopram attenuates increased despair and anxiety-like behavior.•Oxytocin improves differentiation and survival of hippocampal neuronal progenitors.•Reduced BDNF expression in hippocampus was ameliorated by oxytocin.•Loss of PV+ GABA signaling was restored in CA1 but not in CA2/3 by oxytocin.•Itgb3/Chl1 ratio, potential marker of SSRI response, was reduced in our depression model.•Reduction of Itgb3/Chl1 was fully recovered by combined oxytocin/citalopram treatment.
Early diagnosis of autism spectrum disorder (ASD) is crucial for providing appropriate treatments and parental guidance from an early age. Yet, ASD diagnosis is a lengthy process, in part due to the ...lack of reliable biomarkers. We recently applied RNA-sequencing of peripheral blood samples from 73 American and Israeli children with ASD and 26 neurotypically developing (NT) children to identify 10 genes with dysregulated blood expression levels in children with ASD. Machine learning (ML) analyzes data by computerized analytical model building and may be applied to building diagnostic tools based on the optimization of large datasets. Here, we present several ML-generated models, based on RNA expression datasets collected during our recently published RNA-seq study, as tentative tools for ASD diagnosis. Using the random forest classifier, two of our proposed models yield an accuracy of 82% in distinguishing children with ASD and NT children. Our proof-of-concept study requires refinement and independent validation by studies with far larger cohorts of children with ASD and NT children and should thus be perceived as starting point for building more accurate ML-based tools. Eventually, such tools may potentially provide an unbiased means to support the early diagnosis of ASD.
PDF
