Simian virus 40 in humans

Simian virus 40 (SV40) is a monkey virus that was administered to human populations by contaminated vaccines which were produced in SV40 naturally infected monkey cells

Stem Cell Fate and Immunomodulation Promote Bone Regeneration via Composite Bio-Oss®/AviteneTM Biomaterial

Bone defects in maxillofacial regions lead to noticeable deformity and dysfunctions. Therefore, the use of biomaterials/scaffolds for maxillofacial bone regrowth has been attracting great interest from many surgical specialties and experts. Many approaches have been devised in order to create an optimal bone scaffold capable of achieving desirable degrees of bone integration and osteogenesis. Osteogenesis represents a complex physiological process involving multiple cooperating systems. A tight relationship between the immune and skeletal systems has lately been established using the concept of “osteoimmunology,” since various molecules, particularly those regulating immunological and inflammatory processes, are shared. Inflammatory mediators are now being implicated in bone remodeling, according to new scientific data. In this study, a profiler PCR array was employed to evaluate the expression of cytokines and chemokines in human adipose derived-mesenchymal stem cells (hASCs) cultured on porous hydroxylapatite (HA)/Collagen derived Bio-Oss® /Avitene scaffolds, up to day 21. In hASCs grown on the Bio-Oss® /Avitene biomaterial, 12 differentially expressed genes (DEGs) were found to be up-regulated, together with 12 DEG downregulated. Chemokine CCL2, which affects bone metabolism, tested down-regulated. Interestingly, the Bio-Oss® /Avitene induced the down-regulation of pro-inflammatory interleukin IL-6. In conclusion, our investigation carried out on the Bio-Oss® /Avitene scaffold indicates that it could be successfully employed in maxillofacial surgery. Indeed, this composite material has the advantage of being customized on the basis of the individual patients favoring a novel personalized medicine approach

COVID-19 Is a Multifaceted Challenging Pandemic Which Needs Urgent Public Health Interventions

Until less than two decades ago, all known human coronaviruses (CoV) caused diseases so mild that they did not stimulate further advanced CoV research. In 2002 and following years, the scenario changed dramatically with the advent of the new more pathogenic CoVs, including Severe Acute Respiratory Syndome (SARS-CoV-1), Middle Eastern respiratory syndrome (MERS)-CoV, and the new zoonotic SARS-CoV-2, likely originated from bat species and responsible for the present coronavirus disease (COVID-19), which to date has caused 15,581,007 confirmed cases and 635,173 deaths in 208 countries, including Italy. SARS-CoV-2 transmission is mainly airborne via droplets generated by symptomatic patients, and possibly asymptomatic individuals during incubation of the disease, although for the latter, there are no certain data yet. However, research on asymptomatic viral infection is currently ongoing worldwide to elucidate the real prevalence and mortality of the disease. From a clinical point of view, COVID-19 would be defined as “COVID Planet “ because it presents as a multifaceted disease, due to the large number of organs and tissues infected by the virus. Overall, based on the available published data, 80.9% of patients infected by SARS-CoV-2 develop a mild disease/infection, 13.8% severe pneumonia, 4.7% respiratory failure, septic shock, or multi-organ failure, and 3% of these cases are fatal, but mortality parameter is highly variable in dfferent countries. Clinically, SARS-CoV-2 causes severe primary interstitial viral pneumonia and a “cytokine storm syndrome”, characterized by a severe and fatal uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6) with development of endothelitis and generalized thrombosis that can lead to organ failure and death. Risk factors include advanced age and comorbidities including hypertension, diabetes, and cardiovascular disease. Virus entry occurs via binding the angiotensin-converting enzyme 2 (ACE2) receptor present in almost all tissues and organs through the Spike (S) protein. Currently, SARS-CoV-2 infection is prevented by the use of masks, social distancing, and improved hand hygiene measures. This review summarizes the current knowledge on the main biological and clinical features of the SARS-CoV-2 pandemic, also focusing on the principal measures taken in some Italian regions to face

Significant low prevalence of antibodies reacting with simian virus 40 mimotopes in serum samples from patients affected by inflammatory neurologic diseases, including multiple sclerosis

Many investigations were carried out on the association between viruses and multiple sclerosis (MS). Indeed, early studies reported the detections of neurotropic virus footprints in the CNS of patients with MS. In this study, sera from patients affected by MS, other inflammatory (OIND) and non-inflammatory neurologic diseases (NIND) were analyzed for antibodies against the polyomavirus, Simian Virus 40 (SV40). An indirect enzyme-linked immunosorbent assay (ELISA), with two synthetic peptides, which mimic SV40 antigens, was employed to detect specific antibodies in sera from patients affected by MS, OIND, NIND and healthy subjects (HS). Immunologic data indicate that in sera from MS patients antibodies against SV40 mimotopes are detectable with a low prevalence, 6%, whereas in HS of the same mean age, 40 yrs, the prevalence was 22%. The difference is statistically significant (P = 0.001). Significant is also the difference between MS vs. NIND patients (6% vs. 17%; P = 0.0254), whereas no significant difference was detected between MS vs OIND (6% vs 10%; P>0.05). The prevalence of SV40 antibodies in MS patients is 70% lower than that revealed in HS

Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases

Bone metabolism consists of a balance between bone formation and bone resorption, which is mediated by osteoblast and osteoclast activity, respectively. In order to ensure bone plasticity, the bone remodeling process needs to function properly. Mesenchymal stem cells differentiate into the osteoblast lineage by activating different signaling pathways, including transforming growth factor β (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1 (Wnt)/β-catenin pathways. Recent data indicate that bone remodeling processes are also epigenetically regulated by DNA methylation, histone post-translational modifications, and non-coding RNA expressions, such as micro-RNAs, long non-coding RNAs, and circular RNAs. Mutations and dysfunctions in pathways regulating the osteoblast differentiation might influence the bone remodeling process, ultimately leading to a large variety of metabolic bone diseases. In this review, we aim to summarize and describe the genetics and epigenetics of the bone remodeling process. Moreover, the current findings behind the genetics of metabolic bone diseases are also reporte

Indications and visual outcomes of intrastromal corneal ring segment implantation in a large patient series

OBJECTIVES: To describe the indications for and visual outcomes of intrastromal corneal ring segment implantation. METHODS: A large retrospective case-series chart-review study was conducted using Sorocaba Ophthalmological Hospital medical records. This study included 1222 eyes (1196 patients) that were surgically treated between November 2009 and December 2012. The following preoperative data were collected: age, gender, type of medical care and funding source, surgical technique, best-corrected visual acuity, manifest sphere and cylinder refractive error, maximum and minimum central keratometry, and pachymetry measurements of the cornea at the thinnest point and at the ring channel. The postoperative best-corrected visual acuity and patient satisfaction were also determined. The cases were classified into six groups: four keratoconus groups (severe, advanced, moderate and mild), a pellucid marginal degeneration group and a post-graft irregular astigmatism group. This study was approved by the Brazilian Registry of Clinical Trials (UTN number 1111-1182-6181, TRIAL RBR-6S72RF). RESULTS: The age (mean±standard deviation) of the patients was 31.0±10.0 years. The most prevalent pathology was keratoconus (1147 eyes, 93.8%). A correlation was found between ectasia severity and medical assistance (

A Molecular Epidemiology Case Control Study on Pleural Malignant Mesothelioma

Abstract Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure

Serum IgG antibodies from pregnant women reacting to mimotopes of simian virus 40 large T antigen, the viral oncoprotein

Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15-48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates' correction, and Student's t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus

The novel zoonotic COVID-19 pandemic: An expected global health concern

18 years ago, in 2002, the world was astonished by the appearance of Severe Acute Respiratory Syndrome (SARS), supported by a zoonotic coronavirus, called SARS-CoV, from the Guangdong Province of southern China. After about 10 years, in 2012, another similar coronavirus triggered the Middle East Respiratory Syndrome (MERS-CoV) in Saudi Arabia. Both caused severe pneumonia killing 774 and 858 people with 8700 cases of confirmed infection for the former, and 2494 for the latter, causing significant economic losses. 8 years later, despite the MERS outbreak remaining in certain parts of the world, at the end of 2019, a new zoonotic coronavirus (SARS-CoV-2) and responsible of coronavirus Disease (COVID-19), arose from Wuhan, Hubei Province, China. It spread rapidly and to date has killed 3,242 persons with more than 81,000 cases of infection in China and causing over 126,000 global cases and 5,414 deaths in 166 other countries around the world, especially Italy. SARS-CoV-2 would seem to have come from a bat, but the intermediate reservoir continues to be unknown. Nonetheless, as for SARS-CoV and MERS CoV, the Spillover effect linked to animal-human promiscuity, human activities including deforestation, illegal bush-trafficking and bushmeat, cannot be excluded. Recently, however, evidence of inter-human only transmission of SARS-CoV-2 has been accumulated and thus, the outbreak seems to be spreading by human-to-human transmission throughout a large part of the world. Herein we will provide with an update on the main features of COVID-19 and suggest possible solutions how to halt the expansion of this novel pandemic