Recently, LEUNG et al. [1] proposed that α7-subtype nicotinic acetylcholine receptor (α7-nAChR) antagonists might decrease angiotensin-converting enzyme (ACE)2 receptor expression in respiratory epithelium and, hence, prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion of pulmonary epithelial cells. Let us further theoretically evaluate this assertion and contribute to the quest for potential medications that might reduce virulence and pathogenicity of coronavirus disease 2019 (COVID-19). Smoking may be associated with progression and negative outcome of COVID-19 [1]. The receptor-binding domain of the S protein (spike) on the surface of SARS-CoV-2 interacts with the ACE2 receptor, which is an entry point of the virus into host respiratory cells [2]. On the respiratory epithelium cells of smokers and patients with COPD there is higher expression of this "viral receptor" (ACE2 receptor) [1]. Nicotine binds and stimulates nAChR, specifically the α7 subtype, which are localised in lungs and various other tissues, especially in the central nervous system. Increased expression of ACE2 receptors is mediated by stimulation of α7-nAChR. Nicotine, by its agonism on α7-nAChR, might promote entry of SARS-CoV-2 into the respiratory epithelium through ACE2 receptors [1]. Additionally, some evidence suggests that SARS-CoV-2, along with other human coronaviruses, is neurotropic and neurovirulent [3]. Altogether, it is of utmost importance to search for medications that might exert protective effects both at the periphery, at the entry point of SARS-CoV-2 infection, but also in the central nervous system where the virus might propagate.

Bcl-2, the protein product of the Bcl-2 gene, is a member of the Bcl-2 family of proteins that play a crucial role in a complex mechanism of apoptosis. It was recently proposed that bcl-2 could inhibit cancer progression. In this study, we evaluated the expression patterns of Bcl-2, estrogen receptors (ER), progesterone receptors (PR) in 71 primary invasive breast carcinomas and their association with other clinicopathological parameters. Samples from 71 patients with invasive breast cancer with follow-up ranging from 4-103 months (median 57 months) were included in the study. Forty-six patients (66%) obtained a complete response, while 5 (9%) were considered non-responders during the follow up period of 103 months. Eighteen (25%) patients died, 15 (21%) from primary disease and 3 (4%) from other disease. In unvaried analysis, tumor size (<2 cm), lymph node (<4 lymph nodes), hormonal status and Bcl-2 expression are correlated with longer overall (OS) and relapse-free survival (RFS). Patients with 4 or more positive axillary lymph nodes had significantly shorter OS (p=0.01) and RFS (p=0.009). Higher expression of Bcl-2 was associated with longer OS (p=0.02) and RFS (p=0.03), and this result were independent of axillary lymph nodes and tumor size in Cox multivariate analysis.

BackgroundComparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.MethodsRandomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).ResultsSeven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a ‘good’ response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36–3.41; I2 = 48.9) and ‘any’ response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35–3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on ‘any’ response (74.7% v. 65%; RR 1.15; 95% CI 0.82–1.62).ConclusionsAntipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.

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