Publications by authors named "Roberta Rizzo"

162 Publications

The relationship of 3'UTR HLA-G14-bp insertion/deletion and +3142 C/G polymorphisms and soluble HLA-G expression with gynecological cancers: An updated meta-analysis.

Immun Inflamm Dis 2022 07;10(7):e645

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.

Objectives: Human leukocyte antigen-G (HLA-G) is implicated in several cancers and is considered to be an immune checkpoint regulator. We determined the association between polymorphisms in the 3' untranslated region of HLA-G and soluble HLA-G (sHLA-G) expression with gynecological cancers (GCs).

Methods: A meta-analysis was conducted to examine the association between HLA-G14-bp insertion (I)/deletion (D) and +3142C/G polymorphism in GC and to evaluate sHLA-G expression RESULTS: We revealed a significant association between the +3142C/G polymorphism and invasive cervical cancer (ICC) based on the allelic model G versus C (odds ratio [OR] = 0.738, 95% confidence interval [CI] = 0.563-0.966, p = 0.027), dominant GG+GC versus CC (OR = 0.584, 95% CI = 0.395-0.862, p = 0.007), and codominant GG versus CC (OR = 0.527, 95% CI = 0.312-0.891, p = 0.017) models, suggesting that the G allele and GG genotype are protective against ICC. In gynecological precancerous patients with human papillomavirus (HPV) infection, we found that the 14-bp I/D under the codominant DD versus DI model (OR = 0.492, 95% CI = 0.241-1.004, p = 0.051) was of borderline significance. Soluble HLA-G levels were significantly higher in patients compared with healthy controls (standardized mean differences [SMD] = 1.434, 95% CI = 0.442-2.526, p = 0.005). Stratification by cancer type revealed that the sHLA-G levels were significantly increased in cervical cancer (SMD = 4.889, 95% CI = 0.468-9.310, p = 0.030) and in subjects of Asian ethnicity (SMD = 4.889, 95% CI = 0.467-9.309, p = 0.030).

Conclusions: HLA-G14-bp I/D and +3142 C/G polymorphisms are associated with GC and HPV-associated cervical cancer. In addition, we found significantly increased sHLA-G levels in cancer patients. These results provide a basis for further studies in diagnostics and immunotherapy of GC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iid3.645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168547PMC
July 2022

3'UTR-HLA-G polymorphisms and circulating sHLA-G are associated with breast cancer: Evidence from a meta-analysis.

Immunol Lett 2022 Aug 22;248:78-89. Epub 2022 Jun 22.

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:

Background: Human leukocyte antigen-G (HLA-G) gene polymorphisms and circulating sHLA-G have often been linked to the risk of breast cancer (BC). However, the results remain controversial. To resolve this issue, we performed a meta-analysis of HLA-G gene polymorphisms and sHLA-G levels in BC.

Methods: We performed a meta-analysis on the association of HLA-G 14-bp Insertion/Deletion (Ins/Del) and HLA-G +3142 C/G polymorphisms with BC as well as the relationship between sHLA-G and the disease outcome.

Results: Pooled analysis showed a statistically significant association between the HLA-G 14-bp Ins/Del polymorphism and BC susceptibility for the overall population and for Caucasians. The Del allele and genotypes with at least one copy of the Del allele presented significant risks for BC. For HLA-G +3142 C/G polymorphism, the G allele significantly decreased the risk of BC for the overall population and for Caucasians, indicating that the G allele was a protective factor against BC and that the C allele was a significant risk factor for BC. The meta-analysis revealed a significantly increased level of sHLA-G patients with BC compared to the control group for the overall population, Caucasians and Asians.

Conclusion: The present meta-analysis showed a major association of both HLA-G 14-bp Ins/Del and +3142 C/G polymorphisms with BC susceptibility, suggesting Del and C variants as highly significant risk factors for BC. The present study also showed significantly higher sHLA-G levels in patients with BC compared to healthy controls. Our pooled results suggested a critical role of HLA-G in BC, thereby providing evidence to use HLA-G as a biomarker and a therapeutic tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2022.06.010DOI Listing
August 2022

Humoral and adaptive immune responses to the SARS-CoV-2 vaccine.

Int J Infect Dis 2022 Jun 21;122:412-414. Epub 2022 Jun 21.

Respiratory Section, Department of Translational Medicine, University of Ferrara, Italy. Electronic address:

Vaccines against SARS-CoV-2 ameliorate infection and adverse outcomes from SARS-CoV-2. Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination. To assess the relevance of serum levels of SARS-CoV-2 specific antibodies and to further characterize the immune response to SARS-CoV-2 vaccines, we report i) the levels of spike-binding and neutralizing antibodies to SARS-COV-2 in the sera of 30 healthy volunteers at nine months after the second vaccination dose of mRNA vaccine and one month after the booster dose; ii) the levels of IFN-γ production by blood T cells exposed to SARS-CoV-2 spike antigen (Wuhan, Alpha B.1.1.7, Delta B.1.617.2, and Omicron B1.1.529 variants); and iii) the specific phenotype of T cells related with exposure to SARS-CoV-2 spike antigen. We observed that the booster dose induced increased humoral and adaptive immune responses and led to early activation of the memory CD8+ T subset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2022.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214824PMC
June 2022

Competition for dominance within replicating quasispecies during prolonged SARS-CoV-2 infection in an immunocompromised host.

Virus Evol 2022 21;8(1):veac042. Epub 2022 May 21.

Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, P.le Spedali Civili, 1, Brescia 25123, Italy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge for their capability to better adapt to the human host aimed and enhance human-to-human transmission. Mutations in spike largely contributed to adaptation. Viral persistence is a prerequisite for intra-host virus evolution, and this likely occurred in immunocompromised patients who allow intra-host long-term viral replication. The underlying mechanism leading to the emergence of variants during viral persistence in the immunocompromised host is still unknown. Here, we show the existence of an ensemble of minor mutants in the early biological samples obtained from an immunocompromised patient and their dynamic interplay with the master mutant during a persistent and productive long-term infection. In particular, after 222 days of active viral replication, the original master mutant, named MB61, was replaced by a minor quasispecies (MB61) expressing two critical mutations in spike, namely Q493K and N501T. Isolation of the two viruses allowed us to show that MB61 entry into target cells occurred mainly by the fusion at the plasma membrane (PM), whereas endocytosis characterized the entry mechanism used by MB61. Interestingly, coinfection of two human cell lines of different origin with the SARS-CoV-2 isolates highlighted the early and dramatic predominance of MB61 over MB61 replication. This finding may be explained by a faster replicative activity of MB61 as compared to MB61 as well as by the capability of MB61 to induce peculiar viral RNA-sensing mechanisms leading to an increased production of interferons (IFNs) and, in particular, of IFN-induced transmembrane protein 1 (IFITM1) and IFITM2. Indeed, it has been recently shown that IFITM2 is able to restrict SARS-CoV-2 entry occurring by endocytosis. In this regard, MB61 may escape the antiviral activity of IFITMs by using the PM fusion pathway for entry into the target cell, whereas MB61 cannot escape this host antiviral response during MB61 coinfection, since it has endocytosis as the main pathway of entry. Altogether, our data support the evidence of quasispecies fighting for host dominance by taking benefit from the cell machinery to restrict the productive infection of competitors in the viral ensemble. This finding may explain, at least in part, the extraordinary rapid worldwide turnover of VOCs that use the PM fusion pathway to enter into target cells over the original pandemic strain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ve/veac042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129230PMC
May 2022

Investigating Serum sHLA-G Cooperation With MRI Activity and Disease-Modifying Treatment Outcome in Relapsing-Remitting Multiple Sclerosis.

Front Neurol 2022 25;13:872396. Epub 2022 May 25.

Department of Clinical and Experimental Medicine (DMSC), University of Florence, Florence, Italy.

Relapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease in which pathogenesis T cells have a major role. Despite the unknown etiology, several risk factors have been described, including a strong association with human leukocyte antigen (HLA) genes. Recent findings showed that HLA class I-G (HLA-G) may be tolerogenic in MS, but further insights are required. To deepen the HLA-G role in MS inflammation, we measured soluble HLA-G (sHLA-G) and cytokines serum level in 27 patients with RRMS at baseline and after 12 and 24 months of natalizumab (NTZ) treatment. Patients were divided into high (sHLA-G>20 ng/ml), medium (sHLA-G between 10 and 20 ng/ml), and low (sHLA-G <10 ng/ml) producers. Results showed a heterogeneous distribution of genotypes among producers, with no significant differences between groups. A significant decrease of sHLA-G was found after 24 months of NTZ in low producers carrying the +3142 C/G genotype. Finally, 83.3% of high and 100% of medium producers were MRI-activity free after 24 months of treatment, compared to 63.5% of low producers. Of note, we did not find any correlation of sHLA-G with peripheral cell counts or cytokines level. These findings suggest that serum sHLA-G level may partly depend on genotype rather than peripheral inflammation, and that may have impacted on MRI activity of patients over treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2022.872396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174986PMC
May 2022

Increased nuchal translucency can be ascertained using transverse planes.

Am J Obstet Gynecol 2022 Jun 2. Epub 2022 Jun 2.

Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Background: The detection of increased nuchal translucency is crucial for the assessment risk of aneuploidies and other fetal anomalies.

Objective: This study aimed to investigate the ability of a transverse view of the fetal head to detect increased fetal nuchal translucency at 11 to 13 weeks of gestation.

Study Design: This was a prospective study enrolling a nonconsecutive series of women who attended our outpatient clinic from January 2020 to April 2021 for combined screening and were examined by operators certified by the Fetal Medicine Foundation. In each patient, nuchal translucency measurements were obtained both from a median sagittal view and from a transverse view. A second sonologist blinded to the results of the first examination obtained another measurement to assess intermethod and interobsever reproducibility.

Results: A total of 1023 women were enrolled. An excellent correlation was found between sagittal and transverse nuchal translucency measurements, with a mean difference of 0.01 mm (95% confidence interval, -0.01 to 0.02). No systematic difference was found between the 2 techniques. The inter-rater reliability (intraclass correlation coefficient, 0.957; 95% confidence interval, 0.892-0.983) and intrarater reliability (intraclass correlation coefficient, 0.976; 95% confidence interval, 0.941-0.990) of axial measurements were almost perfect. Transverse measurements of 3.0 mm identified all cases with sagittal measurements of ≥3.0 with a specificity of 99.7%; transverse measurements of >3.2 mm identified all cases with sagittal measurements of 3.5 mm with a specificity of 99.7%. The time required to obtain transverse nuchal translucency measurements was considerably shorter than for sagittal measurements, particularly when the fetus had an unfavorable position.

Conclusion: When the sonogram is performed by an expert sonologist, the difference in nuchal translucency measurement obtained with a transverse or sagittal plane is minimal. Increased nuchal translucency can be reliably identified by using transverse views, and in some cases, this may technically be advantageous.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2022.05.057DOI Listing
June 2022

Identification of the most common BRCA alterations through analysis of germline mutation databases: Is droplet digital PCR an additional strategy for the assessment of such alterations in breast and ovarian cancer families?

Int J Oncol 2022 May 6;60(5). Epub 2022 Apr 6.

Epidemiology and Biostatistics Unit, National Cancer Institute IRCCS Fondazione 'G. Pascale', I‑80131 Naples, Italy.

Breast and ovarian cancer represent two of the most common tumor types in females worldwide. Over the years, several non‑modifiable and modifiable risk factors have been associated with the onset and progression of these tumors, including age, reproductive factors, ethnicity, socioeconomic status and lifestyle factors, as well as family history and genetic factors. Of note, BRCA1 and BRCA2 are two tumor suppressor genes with a key role in DNA repair processes, whose mutations may induce genomic instability and increase the risk of cancer development. Specifically, females with a family history of breast or ovarian cancer harboring BRCA1/2 germline mutations have a 60‑70% increased risk of developing breast cancer and a 15‑40% increased risk for ovarian cancer. Different databases have collected the most frequent germline mutations affecting BRCA1/2. Through the analysis of such databases, it is possible to identify frequent hotspot mutations that may be analyzed with next‑generation sequencing (NGS) and novel innovative strategies. In this context, NGS remains the gold standard method for the assessment of BRCA1/2 mutations, while novel techniques, including droplet digital PCR (ddPCR), may improve the sensitivity to identify such mutations in the hereditary forms of breast and ovarian cancer. On these bases, the present study aimed to provide an update of the current knowledge on the frequency of BRCA1/2 mutations and cancer susceptibility, focusing on the diagnostic potential of the most recent methods, such as ddPCR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2022.5349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997337PMC
May 2022

Innate Immune Response in SARS-CoV-2 Infection.

Microorganisms 2022 Feb 23;10(3). Epub 2022 Feb 23.

Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy.

An efficient host immune response is crucial in controlling viral infections. Despite most studies focused on the implication of T and B cell response in COVID-19 (Corona Virus Disease-19) patients or in their activation after vaccination against SARS-CoV-2, host innate immune response has raised even more interest as well. In fact, innate immunity, including Natural Killer (NK) cells, monocytes/macrophages and neutrophils, represent the first line of defense against the virus and it is essential to determine the correct activation of an efficient and specific acquired immune response. In this perspective, we will report an overview on the main findings concerning SARS-CoV-2 interaction with innate host immune system, in correlation with pathogenesis and viral immune escape mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms10030501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950297PMC
February 2022

Herpesvirus Infections in KIR2DL2-Positive Multiple Sclerosis Patients: Mechanisms Triggering Autoimmunity.

Microorganisms 2022 Feb 23;10(3). Epub 2022 Feb 23.

Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.

In multiple sclerosis (MS), there is a possible relationship with viral infection, evidenced by clinical evidence of an implication of infectious events with disease onset and/or relapse. The aim of this research is to study how human herpesvirus (HHVs) infections might dysregulate the innate immune system and impact autoimmune responses in MS. We analyzed 100 MS relapsing remitting patients, in the remission phase, 100 healthy controls and 100 subjects with other inflammatory neurological diseases (OIND) (neuro-lupus) for their immune response to HHV infection. We evaluated NK cell response, levels of HHVs DNA, IgG and pro- and anti-inflammatory cytokines. The results demonstrated that the presence of KIR2DL2 expression on NK cells increased the susceptibility of MS patients to HHV infections. We showed an increased susceptibility mainly to EBV and HHV-6 infections in MS patients carrying the KIR2DL2 receptor and HLA-C1 ligand. The highest HHV-6 viral load was observed in MS patients, with an increased percentage of subjects positive for IgG against HHV-6 in KIR2DL2-positive MS and OIND subjects compared to controls. MS and OIND patients showed the highest levels of IL-8, IL-12p70, IL-10 and TNF-alpha in comparison with control subjects. Interestingly, MS and OIND patients showed similar levels of IL-8, while MS patients presented higher IL-12p70, TNF-alpha and IL-10 levels in comparison with OIND patients. We can hypothesize that HHVs' reactivation, by inducing immune activation via also molecular mimicry, may have the ability to induce autoimmunity and cause tissue damage and consequent MS lesion development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms10030494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954585PMC
February 2022

Overview of the Clinical and Molecular Features of Legionella Pneumophila: Focus on Novel Surveillance and Diagnostic Strategies.

Antibiotics (Basel) 2022 Mar 9;11(3). Epub 2022 Mar 9.

Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.

() is one of the most threatening nosocomial pathogens. The implementation of novel and more effective surveillance and diagnostic strategies is mandatory to prevent the occurrence of legionellosis outbreaks in hospital environments. On these bases, the present review is aimed to describe the main clinical and molecular features of focusing attention on the latest findings on drug resistance mechanisms. In addition, a detailed description of the current guidelines for the disinfection and surveillance of the water systems is also provided. Finally, the diagnostic strategies available for the detection of spp. were critically reviewed, paying the attention to the description of the culture, serological and molecular methods as well as on the novel high-sensitive nucleic acid amplification systems, such as droplet digital PCR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics11030370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944609PMC
March 2022

Inhibitory KIR2DL2 receptor and HHV-8 in classic or endemic Kaposi sarcoma.

Clin Exp Med 2022 Feb 15. Epub 2022 Feb 15.

Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

KIR2DL2, an inhibitory Killer cell Immunoglobulin-like Receptor (KIR), has been shown to predispose to the development of several herpesvirus-associated diseases by inhibiting the efficiency of Natural Killer (NK) cells against virus-infected cells. The aim of this observational study was to assess the prevalence of KIR2DL2 and Human Herpes Virus 8 (HHV8) in patients affected with classical and endemic Kaposi sarcoma (KS), as well as in controls. Blood samples collected from 17 Caucasian, HIV-negative, immunocompetent patients affected with classical KS (c-KS), 12 African, HIV-negative patients with endemic KS (e-KS), 83 healthy subjects and 26 psoriatic patients were processed for genotypization by PCR for two KIR alleles, such as KIR2DL2 and KIR2DL3 and analyzed for HHV-8 presence. The totality of both c-KS and e-KS patients presented HHV-8 infection, whereas HHV8 was found in 26.9% of psoriatic subjects and 19.3% of healthy subjects. KIR2DL2 was found in the 76.5% of c-KS subjects, while the receptor was found in 41.7% of the e-KS group, 34.6% of psoriatic patients and 43.4% of healthy controls (p < 0.0001). A significantly higher prevalence of KIR2DL2 in c-KS patients than in all the other subjects was also confirmed comparing age-matched groups. Based on these results, the inhibitory KIR2DL2 genotype appears to be a possible cofactor which increases the risk of developing c-KS in HHV8-positive, immunocompetent subjects, while it seems less relevant in e-KS pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10238-022-00798-0DOI Listing
February 2022

GlicoPro, Novel Standardized and Sterile Snail Mucus Extract for Multi-Modulative Ocular Formulations: New Perspective in Dry Eye Disease Management.

Pharmaceutics 2021 Dec 13;13(12). Epub 2021 Dec 13.

Chemical, Pharmaceutical and Agricultural Sciences, Department of Chemical, University of Ferrara, 44121 Ferrara, Italy.

This study aimed to evaluate the mucoadhesive and regenerative properties of a novel lubricating multimolecular ophthalmic solution (GlicoPro) extracted from snail mucus and its potential anti-inflammatory and analgesic role in the management of dry eye disease (DED). GlicoPro bio-adhesive efficacy was assessed using a lectin-based assay, and its regenerative properties were studied in a human corneal epithelial cell line. In vitro DED was induced in human corneal tissues; the histology and mRNA expression of selected genes of inflammatory and corneal damage biomarkers were analyzed in DED tissues treated with GlicoPro. A higher percentage of bio-adhesivity was observed in corneal cells treated with GlicoPro than with sodium hyaluronate-based compounds. In the scratch test GlicoPro improved in vitro corneal wound healing. Histo-morphological analysis revealed restoration of cellular organization of the corneal epithelium, microvilli, and mucin network in DED corneal tissues treated with GlicoPro. A significant reduction in inflammatory and ocular damage biomarkers was observed. High-performance liquid chromatography-mass spectrometry analysis identified an endogenous opioid, opiorphin, in the peptide fraction of GlicoPro. In conclusion, GlicoPro induced regeneration and bio-adhesivity in corneal cells; moreover, considering its anti-inflammatory and analgesic properties, this novel ophthalmic lubricating solution may be an innovative approach for the management of DED.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics13122139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708832PMC
December 2021

COVID-19 induced aorto duodenal fistula following evar in the so called "negative" patient.

Vascular 2021 Dec 17:17085381211053695. Epub 2021 Dec 17.

Department of Translational Medicine for Romagna, and Vascular Diseases Center, University of Ferrara, Ferrara, Italy.

Objectives: Since October 2019, SARS-CoV-2 pandemic represents a challenge for the international healthcare system and for the treatment and survival of patients. We normally focus on symptomatic patients, and symptoms can range from the respiratory to the gastrointestinal system. In addition, we consider patients without fever and respiratory symptoms, with both a negative RT nasopharyngeal swab and lung CT, as a "Covid-19 negative patient." In this article, we present a so called Covid-19 "negative" patient, with an unsuspected vascular clinical onset of the viral infection.

Methods: An 80 y.o. man, who previously underwent endovascular aortic repair for an infrarenal abdominal aortic aneurysm, presented to our department with an atypical presentation of an aorto-enteric fistula during the pandemic. While in hospital, weekly nasopharyngeal swab tests were always negative for SARS-CoV-2. However, the absence of aortic endograft complications, the gross anatomy of duodenal ischemic injury, and the recent history of the patient who lived the last months in Bergamo, the Italian city with the highest number of COVID-19 deaths, lead the senior Author to suspect an occult SARS-CoV-2 infection. The patient underwent to resection of the fourth portion of the duodenum and the first jejunal loop, with subsequent duodenum-jejunal latero-lateral anastomosis and the direct suture of the aortic wall. The intestinal specimen was investigated as suspected SARS-CoV-2 bowel infection by the means of immune-histochemistry (IHC). An ileum sample obtained in the pre-COVID-19 era was used as a control tissue.

Results: The histological analysis of the bowel revealed sustained wall ischemia and liponecrosis of the duodenal wall, with intramural blood vessels thrombosis. Blood vessel endotheliitis and neo-angiogenesis were also observed. Finally, the IHC was strongly positive for SARS-CoV-2 RNA and for HLA-G presence, with a particular concentration both in blood vessels and in the intestinal villi. The control tissue sample was not positive for both SARS-CoV-2 and HLA-G.

Conclusions: Coronavirus pandemic continues to be an international challenge and more studies and trials must be done to learn its pathogenesis and its complications. As for thromboembolic events caused by SARS-COV-2, vascular surgeons are involved in treatment and prevention of the complications of this syndrome and must be ready with general surgeons to investigate atypical and particular cases such as the one discussed in this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17085381211053695DOI Listing
December 2021

Synthesis and biological evaluation of novel rhodanine-based structures with antiviral activity towards HHV-6 virus.

Bioorg Chem 2022 02 26;119:105518. Epub 2021 Nov 26.

University of Ferrara, Department of Chemical, Pharmaceutical and Agricultural Sciences, Via Fossato di Mortara, 17, 44121 Ferrara, Italy.

An increased awareness of diseases associated with Human herpesvirus 6 (HHV-6) infection or reactivation has resulted in a growing interest in the evaluation of the best treatment options available for the clinical management of HHV-6 disease. However, no compound has yet been approved exclusively for HHV-6 infection treatment. For this reason, the identification of anti-HHV6 compounds provides a valuable opportunity for developing efficient antiviral therapies. A possible target for antiviral drugs is the virus-cell fusion step. In this study, we synthetized potential fusion intermediates inhibitors based on the rhodanine structure. The obtained derivatives were tested for cytotoxicity and for antiviral activity in human cells infected with HHV6. Level of infection was monitored by viral DNA quantification at different time points up to 7 days post infection. Among the synthetized derivatives, 9e showed a significative inhibitory effect on viral replication that lasted over 7 days, probably attributable to the particular combination of hydrophilic and hydrophobic substituents to the rhodanine moiety. Our results support the use of these amphipathic fusion inhibitors for the treatment of HHV-6 infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.105518DOI Listing
February 2022

Relevance of VEGF and CD147 in different SARS-CoV-2 positive digestive tracts characterized by thrombotic damage.

FASEB J 2021 12;35(12):e21969

Department of Translational Medicine, University of Ferrara, Ferrara, Italy.

Several evidence suggests that, in addition to the respiratory tract, also the gastrointestinal tract is a main site of severe acute respiratory syndrome CoronaVirus 2 (SARS-CoV-2) infection, as an example of a multi-organ vascular damage, likely associated with poor prognosis. To assess mechanisms SARS-CoV-2 responsible of tissue infection and vascular injury, correlating with thrombotic damage, specimens of the digestive tract positive for SARS-CoV-2 nucleocapsid protein were analyzed deriving from three patients, negative to naso-oro-pharyngeal swab for SARS-CoV-2. These COVID-19-negative patients came to clinical observation due to urgent abdominal surgery that removed different sections of the digestive tract after thrombotic events. Immunohistochemical for the expression of SARS-CoV-2 combined with a panel of SARS-CoV-2 related proteins angiotensin-converting enzyme 2 receptor, cluster of differentiation 147 (CD147), human leukocyte antigen-G (HLA-G), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was performed. Tissue samples were also evaluated by electron microscopy for ultrastructural virus localization and cell characterization. The damage of the tissue was assessed by ultrastructural analysis. It has been observed that CD147 expression levels correlate with SARS-CoV-2 infection extent, vascular damage and an increased expression of VEGF and thrombosis. The confirmation of CD147 co-localization with SARS-CoV-2 Spike protein binding on gastrointestinal tissues and the reduction of the infection level in intestinal epithelial cells after CD147 neutralization, suggest CD147 as a possible key factor for viral susceptibility of gastrointestinal tissue. The presence of SARS-CoV-2 infection of gastrointestinal tissue might be consequently implicated in abdominal thrombosis, where VEGF might mediate the vascular damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202100821RRRDOI Listing
December 2021

Transparent Polymeric Formulations Effective against SARS-CoV-2 Infection.

ACS Appl Mater Interfaces 2021 Nov 9;13(46):54648-54655. Epub 2021 Nov 9.

Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara 44100, Italy.

The main route of the transmission of the SARS-CoV-2 virus is through airborne small aerosol particles containing viable virus as well as through droplets transmitted between people within close proximity. Transmission via contaminated surfaces has also been recognized as an important route for the spread of SARS-CoV-2 coronavirus. Among a variety of antimicrobial agents currently in use, polymers represent a class of biocides that have become increasingly important as an alternative to existing biocidal approaches. Two transparent polymeric compounds, containing silver and benzalkonium ions electrostatically bound to a polystyrene sulfonate backbone, were synthesized, through simple procedures, and evaluated for their antimicrobial properties against Gram-positive and Gram-negative bacteria and (ISO EN 1276) and for their antiviral activity toward 229E and SARS-CoV-2 coronaviruses (ISO UNI EN 14476:2019). The results showed that the two tested formulations are able to inhibit the growth of (1.5-5.5) × 10 CFU of Gram-positive bacteria, Gram-negative bacteria, and of the fungal species . Both compounds were able to control the 229E and SARS-CoV-2 infection of a target cell in a time contact of 5 min, with a virucidal effect from 24 to 72 h postinfection, according to the European Medicines Agency (EMA) guidelines, where a product is considered virucidal upon achieving a reduction of 4 logarithms. This study observed a decrease of more than 5 logarithms, which implies that these formulations are likely ideal candidates for the realization of transparent surface coatings that are capable of maintaining remarkable antibacterial activity and SARS-CoV-2 antiviral properties over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c10404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592126PMC
November 2021

Increased sHLA-G Is Associated with Improved COVID-19 Outcome and Reduced Neutrophil Adhesion.

Viruses 2021 09 17;13(9). Epub 2021 Sep 17.

Respiratory Section, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.

Human leukocyte antigen (HLA) is a group of molecules involved in inflammatory and infective responses. We evaluated blood sHLA-E and sHLA-G levels in hospitalized COVID-19 patients with respiratory failure and their relationship with clinical evolution, changes in endothelial activation biomarker profile, and neutrophil adhesion. sHLA-E, sHLA-G, and endothelial activation biomarkers were quantified by ELISA assay in plasma samples. Neutrophil adhesion to endothelium was assessed in the presence/absence of patients' plasma samples. At admission, plasma levels of sHLA-G and sHLA-E were significantly higher in COVID-19 patients with respiratory failure compared to controls. COVID-19 clinical improvement was associated with increased sHLA-G plasma levels. In COVID-19, but not in control patients, an inverse correlation was found between serum sICAM-1 and E-selectin levels and plasma sHLA-G values. The in vitro analysis of activated endothelial cells confirmed the ability of HLA-G molecules to control sICAM-1 and sE-selectin expression via CD160 interaction and FGF2 induction and consequently neutrophil adhesion. We suggest a potential role for sHLA-G in improving COVID-19 patients' clinical condition related to the control of neutrophil adhesion to activated endothelium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13091855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473385PMC
September 2021

TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection.

Microorganisms 2021 Aug 26;9(9). Epub 2021 Aug 26.

Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.

(1) Background: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the coronavirus disease (COVID-19) that has led to a pandemic that began in March 2020. The role of the SARS-CoV-2 components on innate and adaptive immunity is still unknown. We investigated the possible implication of pathogen-associated molecular patterns (PAMPs)-pattern recognition receptors (PRRs) interaction. (2) Methods: We infected Calu-3/MRC-5 multicellular spheroids (MTCSs) with a SARS-CoV-2 clinical strain and evaluated the activation of RNA sensors, transcription factors, and cytokines/interferons (IFN) secretion, by quantitative real-time PCR, immunofluorescence, and ELISA. (3) Results: Our results showed that the SARS-CoV-2 infection of Calu-3/MRC-5 multicellular spheroids induced the activation of the TLR3 and TLR7 RNA sensor pathways. In particular, TLR3 might act via IRF3, producing interleukin (IL)-1α, IL-1β, IL-4, IL-6, and IFN-α and IFN-β, during the first 24 h post-infection. Then, TLR3 activates the NFκB transduction pathway, leading to pro-inflammatory cytokine secretion. Conversely, TLR7 seems to mainly act via NFκB, inducing type 1 IFN, IFN-γ, and IFN-λ3, starting from the 48 h post-infection. (4) Conclusion: We showed that both TLR3 and TLR7 are involved in the control of innate immunity during lung SARS-CoV-2 infection. The activation of TLRs induced pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-4, and IL-6, as well as interferons. TLRs could be a potential target in controlling the infection in the early stages of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9091820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465566PMC
August 2021

Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression, and DNA Methylation Datasets.

Int J Environ Res Public Health 2021 08 17;18(16). Epub 2021 Aug 17.

Epidemiology and Biostatistics Unit, National Cancer Institute-IRCCS 'Fondazione G. Pascale', 80131 Naples, Italy.

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18168697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394939PMC
August 2021

Design of Liposomes Carrying HelixComplex Snail Mucus: Preliminary Studies.

Molecules 2021 Aug 4;26(16). Epub 2021 Aug 4.

Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy.

In recent decades liposomes have been used in different field thanks to their ability to act as a vehicle for a wide range of biomolecules, their great versatility and their easy production. The aim of this study was to evaluate liposomes as a vehicle for the actives present in the HelixComplex (HC) snail mucus for topical delivery. Liposomes composed of a mixture of phosphatidylcholine, cholesterol and octadecylamine were prepared with and without HC (empty liposomes) and their biological efficacy was tested by evaluating cell viability and migration. HC-loaded liposomes (LHC) were stable throughout 60 days of observation, and showed interesting effects on wound healing reconstitution. In particular, we observed that 25 µg/mL LHC were already able to induce a higher cell monolayer reconstitution in comparison to the untreated samples and HC treated samples after only 4 h (28% versus 10% and 7%, = 0.03 and = 0.003, respectively). The effect was more evident at 24 h in comparison with the untreated control (54% versus 21.2% and 41.6%, = 0.006 and = NS, respectively). These results represent a preliminary, but promising, novelty in the delivery strategy of the actives present in the HelixComplex mucus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26164709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399803PMC
August 2021

Bowel ischemia as onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab.

J Intern Med 2022 02 8;291(2):224-231. Epub 2021 Oct 8.

Department of Translational Medicine, University of Ferrara, Ferrara, Italy.

Background: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab.

Methods: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed.

Results: All tested samples were strongly positive for SARS-CoV-2.

Conclusions: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/joim.13385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662187PMC
February 2022

COVID-19 Ocular Prophylaxis: The Potential Role of Ozonated-Oils in Liposome Eyedrop Gel.

Transl Vis Sci Technol 2021 08;10(9)

University of Ferrara, Department of Chemical, Pharmaceutical and Agricultural Sciences, Ferrara, Italy.

Purpose: To assess whether ozonated-oil in liposome eyedrop gel (OED) could be used to prevent the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in an in vitro infection model.

Methods: First, we tested the efficacy of OED on in vitro cell regeneration and dry eye resolution in human corneal epithelial cells (hCE-2). Second, we assessed the in vitro anti-SARS-CoV-2 infection efficacy of OED using Vero E6 cells. Tissues were examined to assess different parameters: morphology, histology, and mRNA expression at 24 hours after treatment.

Results: OED could restore 50% of the scratch in the monolayer of hCE-2 cells in vitro compared with the 25% obtained with phosphate-buffered saline solution (PBS). At 24 hours after treatment with OED, the number of microvilli and the mucin network were restored, as observed using scanning electron microscopy. In Vero E6 cells infected with a primary SARS-CoV-2 strain and treated with OED two times/day, viral replication was found to be inhibited, with a 70-fold reduction observed at 72 hours after infection compared with that under the untreated and PBS-treated conditions.

Conclusions: SARS-CoV-2 transmission through the ocular surface should not be ignored. Although the prevalence of coronavirus disease 2019 conjunctivitis infection is low, the need for a barrier to prevent possible viral infection is warranted. OED treatment may prevent the risk of SARS-CoV-2 infection after 72 hours of twice-daily applications.

Translational Relevance: Dry eye condition might be a risk factor for SARS-CoV-2 infection and OED treatment may have a preventive role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.10.9.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354035PMC
August 2021

Efficacy of personal protective equipment against coronavirus transmission via dental handpieces.

J Am Dent Assoc 2021 08 26;152(8):631-640. Epub 2021 Mar 26.

Background: This laboratory study was done to evaluate the efficacy of personal protective equipment (PPE) and high-volume evacuation (HVE) against the spread of human coronavirus type 229E (HCoV-229E) during a standard dental procedure.

Methods: Patient and operator manikins were used to recreate a dental setting inside a custom-built class III cabinet-like chamber. The mouth of the patient manikin was inoculated with an HCoV-229E suspension, the viral load of which was similar to that of asymptomatic people infected with severe acute respiratory syndrome coronavirus 2. The dental procedure was performed with an air turbine handpiece and HVE for 10 seconds. The efficacy of surgical masks, N95 (filtering facepiece class 2) and filtering facepiece class 3 respirators, and face shields was tested via quantitative real-time polymerase chain reaction.

Results: The wide surface on which the inoculum was spread caused low contamination. Over the external surfaces of masks and respirators, when a face shield was not worn, viral loads ranged from 1.2 through 1.4 log mean gene copies per cm. When the shield was worn, viral loads dropped below the detection limit (< 0.317 log gene copies/cm) for all PPE. On the operator's forehead, viral loads were 0.6 through 0.8 log gene copies/cm. Inside the operator manikin's mouth, viral loads were under the detection limit when using any PPE, with or without the shield. HVE did not significantly change viral loads.

Conclusions: All PPE combinations significantly reduced viral loads in the operator manikin's mouth to below the detection limit, but HVE did not decrease viral contamination.

Practical Implications: Although caution is suggested when removing and disposing of PPE to avoid self-contamination, the combination of PPE and face shields drastically decreases the risk of transmitting human coronavirus during aerosol-generating dental procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.adaj.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997726PMC
August 2021

Viral Load Difference between Symptomatic and Asymptomatic COVID-19 Patients: Systematic Review and Meta-Analysis.

Infect Dis Rep 2021 Jul 16;13(3):645-653. Epub 2021 Jul 16.

Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.

We conducted a systematic review and meta-analysis to investigate the possible difference in the SARS-CoV-2 viral load between asymptomatic and symptomatic COVID-19 patients. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE, Scopus, Web of Science and Google Scholar for all investigations in the English language, reporting data on the threshold cycle (C) from real-time RT-PCR assays for the RNA-dependent RNA polymerase (), envelope () and nucleocapsid () SARS-CoV-2 genes in asymptomatic and symptomatic COVID-19 patients. Results: Overall, 703 COVID-19 patients (553 symptomatic and 150 asymptomatic) were analyzed. Five investigations reported the mean age of patients, evidencing that asymptomatic patients were younger than symptomatic patients (34.0 vs. 40.3 years, respectively). Pooled data regarding the levels of expression of the gene revealed no significant difference between symptomatic and asymptomatic subjects. Similarly, no differences were observed comparing the mean C values for the and genes. Based on real-time RT-PCR data, no differences exist in the viral load between symptomatic and asymptomatic COVID-19 subjects considering C values for , and genes' expression. Asymptomatic subjects may represent a reservoir of the infection and significantly contribute to the maintenance of the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/idr13030061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293148PMC
July 2021

Prognostic significance of high circulating sHLA-G in ovarian carcinoma.

HLA 2021 10 26;98(4):357-365. Epub 2021 Jul 26.

Laboratory Microorganismes and Active Biomolecules, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.

HLA-G is a non-classical major histocompatibility complex class Ib molecule. Its expression has been described in various cancer types, including ovarian cancer. HLA-G molecule has been implicated in immune escape and in progression of ovarian tumor cells. Our goal was to assess if total soluble (s)HLA-G molecules or HLA-G5 and sHLA-G1 isoforms could be considered as circulating ovarian tumor biomarkers, we measured the concentration of these molecules in ovarian carcinoma patients stratified according with their clinicopathological parameters. sHLA-G, sHLA-G1 and HLA-G5 concentrations were dosed in plasma samples by sandwich-ELISA. The sHLA-G dimerization was analyzed after immunoprecipitation and SDS-PAGE migration. Total sHLA-G and sHLA-G1 levels were significantly represented in plasma of ovarian carcinoma patients compared to healthy controls. sHLA-G1 isoform concentration was highly represented in ovarian carcinoma compared to HLA-G5 isoforms. Additionally, high sHLA-G molecules have been found in aged patients, as well as in patients with advanced stages, and those with metastatic lymph nodes and those with distant metastasis. Elsewhere, sHLA-G monomers were highly represented in ovarian carcinoma patients compared to controls. sHLA-G plasmatic protein was highly represented in ovarian carcinoma. In effect, HLA-G might be considered as a new checkpoint molecule that could be used to assess progression and recurrence of the disease, thus placing it as a potential biomarker for advanced and complicated ovarian carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tan.14374DOI Listing
October 2021

Late-onset intrauterine growth restriction and HHV-6 infection: A pilot study.

J Med Virol 2021 11 24;93(11):6317-6322. Epub 2021 Jun 24.

Department of Medical Sciences,Obstetric and Gynecological Clinic, University of Ferrara, Ferrara, Italy.

Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections having been associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.27138DOI Listing
November 2021

Human Herpesviruses 6A and 6B in Reproductive Diseases.

Front Immunol 2021 25;12:648945. Epub 2021 Mar 25.

Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

Human herpesviruses 6A (HHV-6A) and human herpesvirus 6B (HHV-6B)-collectively, HHV-6A/B-are recently-discovered but ancient human viruses. The vast majority of people acquire one or both viruses, typically very early in life, producing an ineradicable lifelong infection. The viruses have been linked to several neurological, pulmonary and hematological diseases. In early human history, the viruses on multiple occasions infected a germ cell, and integrated their DNA into a human chromosome. As a result, about 1% of humans are born with the full viral genome present in every cell, with uncertain consequences for health. HHV-6A may play a role in 43% of cases of primary unexplained infertility. Both the inherited and acquired viruses may occasionally trigger several of the factors that are important in the pathogenesis of preeclampsia. Transplacental infection occurs in 1-2% of pregnancies, with some evidence suggesting adverse health consequences for the child. While emerging knowledge about these viruses in reproductive diseases is not sufficient to suggest any changes in current practice, we write this review to indicate the need for further research that could prove practice-changing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.648945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027340PMC
September 2021

Embryo morphokinetic score is associated with biomarkers of developmental competence and implantation.

J Assist Reprod Genet 2021 Jul 5;38(7):1737-1743. Epub 2021 Apr 5.

9.baby Family and Fertility Center, Via Dante, 15, 40125, Bologna, Italy.

Purpose: To study embryo morphokinetics in relation to release in spent media of molecules with possible roles in development and implantation (miR-20a, miR-30c, and sHLA-G).

Methods: Data were obtained from embryos generated in standard IVF and ICSI cycles. The Eeva system was used for embryo assessment, based on early morphokinetic parameters and producing a score (1-5, best-worst) corresponding to higher/medium/lower chances of development to blastocyst. miRNAs - mm miR-20a-5p and miR-30c-5p - and sHLA-G were quantified in 25 μl of spent blastocyst media (SBM) collected before vitrification or transfer. Statistical analyses were performed applying Kolmogorov-Smirnov, Shapiro-Wilk, and Spearman's correlation coefficient tests, where appropriate.

Results: SBM were collected from a total of 172 viable blastocysts. Their analysis showed that concentration of miR-20a was progressively lower as Eeva score increased and probability of development to blastocyst decreased (P = 0.016). The opposite trend was observed in the case of miR-30c, i.e., concentration was higher as score increased and chances of development to blastocyst decreased (P = 0.004). Analysis of sHLA-G revealed a negative correlation with Eeva score, i.e., levels were progressively lower as Eeva score increased and probability of development to blastocyst decreased (R = - 0.388, N = 141, P = 0.001).

Conclusion: Our data suggest that morphokinetic algorithms that predict development to blastocyst stage, in fact, also identify embryos with molecular and cellular profiles more consistent with developmental functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-021-02162-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324755PMC
July 2021

Sylvian fossa sonographic measurements in 18 to 23 weeks fetuses with and without cerebral malformations.

Am J Obstet Gynecol MFM 2021 07 21;3(4):100357. Epub 2021 Mar 21.

Obstetric Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital (Drs Montaguti, Rizzo, Livi, and Salsi and Pilu).

Background: Abnormal sulcation of the brain is frequently associated with severe malformations, but the prenatal diagnosis is challenging, especially in early pregnancy.

Objective: Our study aimed to investigate the value of Sylvian fossa sonographic biometry in the diagnosis of cerebral malformation in the second trimester of gestation.

Study Design: We prospectively established the normal values of the Sylvian fossa depth in a cohort of nonconsecutive patients, with singleton pregnancies and normal fetuses between 18+0 and 23+0 weeks' gestation. For each patient, a coronal view of the fetal brain, with a clear visualization of the anterior complex and the Sylvian fissure, was acquired by 1 sonologist, who also measured the depth of the fossa. Reproducibility for each parameter was assessed by a second sonologist using stored images. We also retrospectively acquired the same measurements in second trimester fetuses with central nervous system anomalies.

Results: In 103 fetuses with a normal sonogram, the mean depth of the Sylvian fossa was 3.9±0.8 mm Interobserver reproducibility analysis demonstrated good results. Notably, 11 of 31 fetuses with cerebral malformations had a Sylvian fossa depth of <-2 z-scores, and these were found to have malformations of cortical development, lissencephaly in particular, or microcephaly.

Conclusion: Sonographic measurement of the Sylvian fossa during second trimester is feasible and reproducible. A shallow Sylvian fossa is associated with malformations of cortical development, microcephaly, or both.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajogmf.2021.100357DOI Listing
July 2021

Aerosols modification with HO reduces airborne contamination by dental handpieces.

J Oral Microbiol 2021 Jan 29;13(1):1881361. Epub 2021 Jan 29.

Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.

: We designed an study to evaluate the efficiency of an 0.5 vol% hydrogen peroxide-based spray in reducing Coronavirus 229E spread during a conventional dental procedure. : A class III cabinet-like chamber was custom-built, using phantoms for both patient and operator. A suspension of HCoV-229E in artificial saliva having a similar viral load to SARS-CoV-2 asymptomatic patients was inoculated inside the patient's phantom mouth. A 10 s-lasting dental procedure was performed using an aerosol-generating air-turbine, with or without high-volume evacuation (HVE). The effect of 0.5 vol% HO cooling spray in reducing viral loads was tested. Viral presence on the operator phantom was assessed by Real-Time quantitative PCR on the mask's outer surface, on the phantom's forehead, and inside its mouth. : When the HO cooling spray was used, as compared to the conventional spray, viral loads were significantly lower on all tested sites, falling below the detection limit. Viral loads did not significantly change in any tested site when HVE was used. : The use of 0.5 vol% HO cooling spray by dental handpieces drastically reduced the possibility of coronaviruses spread during aerosol-generating dental procedures. This strategy deserves further consideration among the preventive measures to be adopted during the SARS-CoV-2 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20002297.2021.1881361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850367PMC
January 2021
-->