Prostate cancer frequently metastasizes to the bone, and the interaction between cancer cells and bone microenvironment has proven to be crucial in the establishment of new metastases. Bone marrow mesenchymal stem cells (BM-MSCs) secrete various cytokines that can regulate the behaviour of neighbouring cell. However, little is known about the role of BM-MSCs in influencing the migration and the invasion of prostate cancer cells. We hypothesize that the stromal cell-derived factor-1α released by BM-MSCs may play a pivotal role in these processes. To study the interaction between factors secreted by BM-MSCs and prostate cancer cells we established an in vitro model of transwell co-culture of BM-MSCs and prostate cancer cells DU145. Using this model, we have shown that BM-MSCs produce soluble factors which increase the motility of prostate cancer cells DU145. Neutralization of stromal cell-derived factor-1α (SDF1α) via a blocking antibody significantly limits the chemoattractive effect of bone marrow MSCs. Moreover, soluble factors produced by BM-MSCs greatly activate prosurvival kinases, namely AKT and ERK 1/2. We provide further evidence that SDF1α is involved in the interaction between prostate cancer cells and BM-MSCs. Such interaction may play an important role in the migration and the invasion of prostate cancer cells within bone.

Although coronaviruses (CoVs) have long been predicted to cause zoonotic diseases and pandemics with high probability, the lack of effective anti-pan-CoVs drugs rapidly usable against the emerging SARS-CoV-2 actually prevented a promptly therapeutic intervention for COVID-19. Development of host-targeting antivirals could be an alternative strategy for the control of emerging CoVs infections, as they could be quickly repositioned from one pandemic event to another. To contribute to these pandemic preparedness efforts, here we report on the broad-spectrum CoVs antiviral activity of MEDS433, a new inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 inhibited the in vitro replication of hCoV-OC43 and hCoV-229E, as well as of SARS-CoV-2, at low nanomolar range. Notably, the anti-SARS-CoV-2 activity of MEDS433 against SARS-CoV-2 was also observed in kidney organoids generated from human embryonic stem cells. Then, the antiviral activity of MEDS433 was reversed by the addition of exogenous uridine or the product of hDHODH, the orotate, thus confirming hDHODH as the specific target of MEDS433 in hCoVs-infected cells. Taken together, these findings suggest MEDS433 as a potential candidate to develop novel drugs for COVID-19, as well as broad-spectrum antiviral agents exploitable for future CoVs threats.

The synthesis of α-fluorinated methyl ketones has always been challenging. New methods based on the homologation chemistry via nucleophilic halocarbenoid transfer, carried out recently in our labs, allowed us to design and synthesize a target-directed dipeptidyl α,α-difluoromethyl ketone (DFMK) 8 as a potential antiviral agent with activity against human coronaviruses. The ability of the newly synthesized compound to inhibit viral replication was evaluated by a viral cytopathic effect (CPE)-based assay performed on MCR5 cells infected with one of the four human coronaviruses associated with respiratory distress, i.e., hCoV-229E, showing antiproliferative activity in the micromolar range (EC₅₀ = 12.9 ± 1.22 µM), with a very low cytotoxicity profile (CC₅₀ = 170 ± 3.79 µM, 307 ± 11.63 µM, and 174 ± 7.6 µM for A549, human embryonic lung fibroblasts (HELFs), and MRC5 cells, respectively). Docking and molecular dynamics simulations studies indicated that 8 efficaciously binds to the intended target hCoV-229E main protease (M^pro). Moreover, due to the high similarity between hCoV-229E M^pro and SARS-CoV-2 M^pro, we also performed the in silico analysis towards the second target, which showed results comparable to those obtained for hCoV-229E M^pro and promising in terms of energy of binding and docking pose.

Background: Data about acute poisoning in Italian pediatric patients are obsolete or absent. This study would partially fill this exiting gap and compare the scene with others around the world. Methods: A retrospective evaluation was performed on a 2012–2017 data registry of the Children’s Emergency Department at the Regina Margherita Hospital of Turin, where 1030 children under age 14 were accepted with a diagnosis of acute intoxication. Results: The median age of the patients was 2.2 years (IQR 2.3) and 55% were male. Events occurred mostly in children aged 1–4 years (n = 751, 72.9%). Six hundred and eight patients (59%) were exposed to Nonpharmaceutical agents, the household cleaning products being the more frequent (n = 298, 49%). Exposure to Pharmaceuticals were 422 (41%); the most common Pharmaceuticals were analgesics (n = 88, 20.8%), psychotropics (n = 77, 18.2%) and cardiovascular (n = 53, 12.6%) drugs. The 85% of the intoxications occurred accidentally, the 10.6% as therapeutic error, the 2.3% as suicide attempts and the 1.5% for recreational purposes. No patient died. Conclusions: Despite acute poisoning being a relevant problem in pediatric emergency, our results would seem to paint a less worrying picture if compared to other countries, mainly when considering the children hospitalized in the pediatric intensive care unit and the number of deaths. Nevertheless, our study might represent a tool for public health authorities to program incisive interventions.

Background: Orthopedic surgical-site infection (SSI), mostly due to S. aureus, is recognized as a major adverse event. This research aims to verify the usefulness of surgical team decolonization in order to reduce the risk of surgical-site infection. Materials and methods: We performed swabs of both nares and oropharynx to identify S. aureus carriers among orthopedic team members who consented to cooperate with the study. Carriers were treated with local application of mupirocin ointment. Results: Retrospective study of 1,000 consecutive patients operated before surgical team decolonization showed 6‰ SSIs. Of the 300 cases considered after decolonization, none developed SSI. Conclusions: Though we are aware that more data need to be collected, this work might be relevant for the introduction of a new preventive protocol.

The global onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections happened suddenly, hence imposing a rapid definition of effective therapeutic approaches. Antibiotics were included among the prophylactic agents because of both the similarity between SARS-CoV-2 and atypical pneumonia symptoms, and the immune-modulating and anti-inflammatory properties of such drugs. Although, this approach could exacerbate the emergence of antimicrobial resistance. To evaluate the impact of the COVID-19 pandemic on the spread and characteristics of bacterial infections, as well as on the frequency of antimicrobial resistance, we investigated and compared clinical bacterial strains isolated in an Italian hospital from COVID-19 patients and non-COVID-19 patients during and before the COVID-19 outbreak. Data clearly indicate the impact of the COVID-19 pandemic on bacterial infections: not only some bacterial species were found in either COVID-19 positive or in COVID-19 negative patients, but isolates from COVID-19 patients also showed higher levels of antimicrobial resistance. Nevertheless, despite some bacterial species were isolated only before or over the pandemic, no differences were observed among the antimicrobial resistance levels. Overall, these results recapitulate the current situation of microbial infections and could also provide an overview of the impact of COVID-19 on bacterial pathogens spread and resistance.