Nanostructures for prevention, diagnosis, and treatment of viral respiratory infections: from influenza virus to SARS-CoV-2 variants.

Viruses are a major cause of mortality and socio-economic downfall despite the plethora of biopharmaceuticals designed for their eradication. Conventional antiviral therapies are often ineffective. Live-attenuated vaccines can pose a safety risk due to the possibility of pathogen reversion, whereas inactivated viral vaccines and subunit vaccines do not generate robust and sustained immune responses. Recent studies have demonstrated the potential of strategies that combine nanotechnology concepts with the diagnosis, prevention, and treatment of viral infectious diseases. The present review provides a comprehensive introduction to the different strains of viruses involved in respiratory diseases and presents an overview of recent advances in the diagnosis and treatment of viral infections based on nanotechnology concepts and applications. Discussions in diagnostic/therapeutic nanotechnology-based approaches will be focused on H1N1 influenza, respiratory syncytial virus, human parainfluenza virus type 3 infections, as well as COVID-19 infections caused by the SARS-CoV-2 virus Delta variant and new emerging Omicron variant.

Antioxidant Defense Capacity Is Reduced in Thyroid Stem/Precursor Cells Compared to Differentiated Thyrocytes.

There is much evidence linking oxidative stress to thyroid cancer, and stem cells are thought to play a key role in the tumor-initiating mechanism. Their vulnerability to oxidative stress is unexplored. This study aimed to comparatively evaluate the antioxidant capacity of stem/precursor thyroid cells and mature thyrocytes. Human stem/precursor cells and mature thyrocytes were exposed to increasing concentrations of menadione, an oxidative-stress-producing agent, and reactive oxygen species (ROS) production and cell viability were measured. The expression of antioxidant and detoxification genes was measured via qPCR as well as the total antioxidant capacity and the content of glutathione. Menadione elevated ROS generation in stem/precursor thyroid cells more than in mature thyrocytes. The ROS increase was inversely correlated (p = 0.005) with cell viability, an effect that was partially prevented by the antioxidant curcumin. Most thyroid antioxidant defense genes, notably those encoding for the glutathione-generating system and phase I detoxification enzymes, were significantly less expressed in stem/precursor thyroid cells. As a result, the glutathione level and the total antioxidant capacity in stem/precursor thyroid cells were significantly decreased. This reduced antioxidant defense may have clinical implications, making stem/precursor thyroid cells critical targets for environmental conditions that are not detrimental for differentiated thyrocytes.

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy.

In late 2019, a new member of the Coronaviridae family, officially designated as "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.

Energy and New Economic Approach for Nearly Zero Energy Hotels.

The paper addresses an important long-standing question in regards to the energy efficiency renovation of existing buildings, in this case hotels, towards nearly zero-energy (nZEBs) status. The renovation of existing hotels to achieve a nearly zero-energy (nZEBs) performance is one of the forefront goals of EU's energy policy for 2050. The achievement of nZEBs target for hotels is necessary not only to comply with changing regulations and legislations, but also to foster competitiveness to secure new funding. Indeed, the nZEB hotel status allows for the reduction of operating costs and the increase of energy security, meeting the market and guests' expectations. Actually, there is not a set national value of nZEBs for hotels to be attained, despite the fact that hotels are among the most energy-intensive buildings. This paper presents the case study of the energy retrofit of an existing historical hotel located in southern Italy (Syracuse) in order to achieve nZEBs status. Starting from the energy audit, the paper proposes a step-by-step approach to nZEBs performance, with a perspective on the costs, in order to identify the most effective energy solutions. Such an approach allows useful insights regarding energy and economic-financial strategies for achieving nZEBs standards to highlighted. Moreover, the results of this paper provide, to stakeholders, useful information for quantifying the technical convenience and economic profitability to reach an nZEBs target in order to prevent the expenses necessary by future energy retrofit programs.

HIV Vaccination: A Roadmap among Advancements and Concerns.

Since the identification of the Human Immunodeficiency Virus type 1 (HIV-1) as the etiologic agent of AIDS (Acquired Immunodeficiency Syndrome), many efforts have been made to stop the AIDS pandemic. A major success of medical research has been the development of the highly active antiretroviral therapy and its availability to an increasing number of people worldwide, with a considerable effect on survival. However, a safe and effective vaccine able to prevent and eradicate the HIV pandemic is still lacking. Clinical trials and preclinical proof-of-concept studies in nonhuman primate (NHP) models have provided insights into potential correlates of protection against the HIV-1 infection, which include broadly neutralizing antibodies (bnAbs), non-neutralizing antibodies targeting the variable loops 1 and 2 (V1V2) regions of the HIV-1 envelope (Env), polyfunctional antibody, and Env-specific T-cell responses. In this review, we provide a brief overview of different HIV-1 vaccine approaches and discuss the current understanding of the cellular and humoral correlates of HIV-1 immunity.

E2 multimeric scaffold for vaccine formulation: immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells.

BACKGROUND: The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. RESULTS: The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4(+) and CD8(+) cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. CONCLUSIONS: The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

Analysis of SEMA6B gene expression in breast cancer: identification of a new isoform.

BACKGROUND: SEMA6B is a member of the semaphorins axon-guidance family. A growing body of evidence has been accumulated describing the role of semaphorin molecules in cancer development and the involvement of SEMA6B in cancer progression has recently been proposed. METHODS: Our analysis, based on real-time PCR, focused on the expression of SEMA6B in a panel of breast cancer tissues, compared to the normal counterpart. RESULTS: In cancer tissues we found a significantly strong down-modulation of this transcript. Moreover we identified and characterized a novel SEMA6B isoform, named SEMA6Ba. This isoform has a novel splice junction, created by the usage of alternative donor and acceptor splice sites internal to the exon 17. By in silico analysis we found that the new transcript 3' UTR lacks some highly-conserved miRNA binding sites, suggesting possible consequences on both spatial and temporal expression of SEMA6Ba. The translated sequence of SEMA6Ba lacks the cytoplasmic tail, crucial for triggering the reverse signaling described for the transmembrane semaphorins. We also demonstrated, by immunofluorescence analysis of endogenous and overexpressed SEMA6Ba, that the protein clearly localized to the endoplasmic reticulum and plasma membrane. In conclusion, SEMA6B gene products are strongly down modulated in breast cancer tissues and a new isoform named SEMA6Ba has been described and characterized. GENERAL SIGNIFICANCE: Our work states a clear relation among breast cancer and SEMA6B expression; moreover we describe for the first time the SEMA6Ba protein and report here the analysis of SEMA6Ba RNA messenger, the protein expression and the cellular localization.

Is BCLC algorithm useful in clinical practice? Study on 164 HCC patients.

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification has been recently validated as the best system for treatment guidance for hepatocellular carcinoma (HCC). The aim of this retrospective study is to evaluate the usefulness of BCLC in the treatment of HCC comparing our treatment decision and the BCLC algorithm indications. METHODOLOGY: In 102 patients affected by HCC observed from 1991 to 2002 a retrospective analysis was performed. The choice of treatment was compared with the treatment schedule proposed by BCLC. Whereas the second group of 62 patients observed from 2008 to 2010 was analysed both retrospectively in comparison with the BCLC classification. RESULTS: We found a disagreement in between our decision making and the choices suggested by BCLC. We only found a statistical significance for age and performance status test. In surgical patients the median age and the PST class were lower with a statistically significant p value (0.04 and 0.03, respectively). CONCLUSIONS: The BCLC system would not have changed our decision either in the past, or in present days, especially in surgical indications. Even if the decision making is affected by BCLC, actually that process still needs the support of the experience of each clinical centre involved.

Ileocolonic anastomosis: preferred techniques in 999 patients. A multicentric study.

PURPOSE: There is no standard anastomosis technique for performing reconstruction after right hemicolectomy, and, in the literature, studies on ileocolonic anastomosis are rare. The aim of this retrospective work was to analyze the type of anastomosis techniques used and the related results in a multicentric enquiry. METHODS: A questionnaire was sent to the departments of surgery covering a 1.8 million inhabitant area to collect data concerning the anastomosis techniques used and the results related to complications. RESULTS: Data for 999 patients from 14 departments of surgery were collected. 95.8% of the patients were affected by cancer and 4.2% were affected by inflammatory bowel disease (IBD). The positioning of the anastomosing bowel was side-to-side in 60.5% of the patients, end-to-side (E-S) in 38.1% of the patients and end-to-end in 1.3% of the patients. 46.4% of the anastomoses were handsewn and 53.6% were stapled. The complication rate in the cancer group was 5.1% for handsewn techniques and 4.7% for stapled techniques. The rate of anastomotic leakage was higher in the handsewn group than that in the stapled group (P < 0.05). The data for the IBD group were not statistically relevant. CONCLUSIONS: This wide multicentric retrospective analysis showed that there remains variability in ileocolonic anastomosis techniques. Stapled anastomoses are associated with a lower incidence of leakage. In stapled anastomoses, the E-S configuration is also related to a lower incidence of leakage.

Medical Applications of Molecular Biotechnologies in the Context of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a gender autoimmune disease that is manifested by chronic inflammation of the thyroid. Clinical trial studies (CTSs) use molecular biotechnologies (MB) to approach HT appearance. The aims of this study were to analyze the applications of MB in CTSs carried out in HT populations (HT-CTSs). Further, to evaluate the role of MB in the context of the hygiene hypothesis (HH). From 75 HT-CTSs found at clinicaltrials.gov web place, forty-five were considered for this investigation. Finally, six HT-CTSs were reported as molecular HT-CTSs (mHT-CTSs) because these were planning to utilize MB. Two of mHT-CTSs were programmed on the French population to isolate DNA viral sequences. Blood, urine, and thyroid tissue biospecimens were analyzed to pick out the parvo and polyoma viruses. Two mHT-CTSs carried out in China aimed to identify oral and fecal microbiotas by measuring PCR sequencing of the 16S rRNA gene. Two mHT-CTSs were programmed in the USA and Greece, respectively, for interception of DNA polymorphisms to associate with genetic susceptibility to HT. In conclusion, MB are mainly employed in HT-CTSs for infective pathogenesis and genetic fingerprinting of HT. Furthermore, MB do not provide evidence of HH; however, they are useful for providing direct evidence of the presence of viruses.

Understanding Syrian migration in Lebanon: a methodological framework.

Background: Wars, crises, and climate change are just a few of the worldwide concerns that have resulted in the forced relocation of millions of people. After 12 years of conflict in Syria, millions of Syrians are still displaced in the neighbouring countries, and their conditions have worsened due to the economic and socio-political crisis of the region. This paper reports on a study conducted in Lebanon as part of the EU Horizon-funded project ADMIGOV - Advancing Alternative Migration Governance. It describes the methodological framework used to study Syrian migration in Lebanon and sheds light on the phenomenon's patterns, challenges, and impacts. Methods: In our study, we opted for a mixed method. It is built on a large corpus of primary data collected over the course of years of intensive, in-depth fieldwork and the author's immersion in the community. Alongside observations, quantitative and qualitative phone interviews were conducted to obtain the perceptions of displaced Syrians living in informal tented settlements in rural Lebanon and an incomplete building in the city of Saida. This interview data is accompanied by primary and secondary data sources, including the findings of other European research projects, statistics from UNHCR and IOM, and academic and press articles. Results: Our research revealed the difficulties Syrians displaced in Lebanon encounter while navigating the challenging situation they are trapped in. Based on a case study approach, it unveils similarities and differences determined by the government's no encampment policy that led to self-settled practices across the country. This approach helped in understanding the challenging dynamic created by weak public institutions and their failure to guarantee the observance of basic human rights, compromising displaced Syrians safety. The weakness of public institutions and their failure to guarantee the observance of basic human rights has compromised displaced safety. Moreover, even though the development interventions and aid assistance have been necessary for Syrians' survival, they proved insufficient, and unequally distributed by location evidencing the inefficiencies of the majority of development aid projects. Conclusions: The findings contribute to an enriched understanding of the situation of Syrians in Lebanon and offer insights for policymakers, practitioners, and researchers working in the field of forced migration and humanitarian responses.

Since the war began in 2011, more than 6.8 million Syrians have been displaced inside their own country, and another 5.5 million fled to neighbouring countries for safety ( UNHCR, 2023a). This study examines the forces contributing to the protracted displacement of Syrians in Lebanon and limiting the agency of displaced individuals. It explores the relationship between Syrian migration trends, socio­economic and political constraints and development interventions in the country to shed light on how these factors have shaped displaced vulnerability and marginalisation and influenced the deciding factors behind the migration or return decision. Moreover, the research looks at the plight of Syrian refugees in Lebanon, emphasising how they are spatially marginalised and segregated from urban, peri-urban, and rural areas. Therefore, it investigates how Syrian refugees manage to make ends meet in the cramped conditions of their transitory homes on the peripheries of several urban clusters. Our research was informed by mapping activities, a literature review, and quantitative and qualitative interviews. The Bekaa Valley, with the horizontal expansion of Informal Tented Settlements (ITSs) on agricultural fields and the coast, specifically the city of Saida, were chosen as a case study. The research is part of the EU Horizon-funded project titled ADMIGOV ­ Advancing Alternative Migration Governance.

Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells.

Tumor-associated antigens (TAAs) represent attractive targets in the development of anti-cancer vaccines. The filamentous bacteriophage is a safe and versatile delivery nanosystem, and recombinant bacteriophages expressing TAA-derived peptides at a high density on the viral coat proteins improve TAA immunogenicity, triggering effective in vivo anti-tumor responses. To enhance the efficacy of the bacteriophage as an anti-tumor vaccine, we designed and generated phage particles expressing a CD8+ peptide derived from the human cancer germline antigen NY-ESO-1 decorated with the immunologically active lipid alpha-GalactosylCeramide (α-GalCer), a potent activator of invariant natural killer T (iNKT) cells. The immune response to phage expressing the human TAA NY-ESO-1 and delivering α-GalCer, namely fdNY-ESO-1/α-GalCer, was analyzed either in vitro or in vivo, using an HLA-A2 transgenic mouse model (HHK). By using NY-ESO-1-specific TCR-engineered T cells and iNKT hybridoma cells, we observed the efficacy of the fdNY-ESO-1/α-GalCer co-delivery strategy at inducing activation of both the cell subsets. Moreover, in vivo administration of fdNY-ESO-1 decorated with α-GalCer lipid in the absence of adjuvants strongly enhances the expansion of NY-ESO-1-specific CD8+ T cells in HHK mice. In conclusion, the filamentous bacteriophage delivering TAA-derived peptides and the α-GalCer lipid may represent a novel and promising anti-tumor vaccination strategy.

Booster Dose of SARS-CoV-2 mRNA Vaccine in Kidney Transplanted Patients Induces Wuhan-Hu-1 Specific Neutralizing Antibodies and T Cell Activation but Lower Response against Omicron Variant.

Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Although several studies reported antibody production in KTR after vaccination, data related to immunity to the Omicron (B.1.1.529) variant are sparse. Herein, we analyzed anti-SARS-CoV-2 immune response in seven KTR and eight healthy controls after the second and third dose of the mRNA vaccine (BNT162b2). A significant increase in neutralizing antibody (nAb) titers were detected against pseudoviruses expressing the Wuhan-Hu-1 spike (S) protein after the third dose in both groups, although nAbs in KTR were lower than controls. nAbs against pseudoviruses expressing the Omicron S protein were low in both groups, with no increase after the 3rd dose in KTR. Reactivity of CD4+ T cells after boosting was observed when cells were challenged with Wuhan-Hu-1 S peptides, while Omicron S peptides were less effective in both groups. IFN-γ production was detected in KTR in response to ancestral S peptides, confirming antigen-specific T cell activation. Our study demonstrates that the 3rd mRNA dose induces T cell response against Wuhan-Hu-1 spike peptides in KTR, and an increment in the humoral immunity. Instead, humoral and cellular immunity to Omicron variant immunogenic peptides were low in both KTR and healthy vaccinated subjects.

Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants.

The efficacy of a new vaccine-delivery vector, based on the filamentous bacteriophage fd displaying a single-chain antibody fragment known to bind the mouse DC surface molecule DEC-205, is reported. We demonstrate both in vitro and in vivo an enhanced receptor-mediated uptake of phage particles expressing the anti-DEC-205 fragment by DCs. We also report that DCs targeted by fd virions in the absence of other stimuli produce IFN-α and IL-6, and acquire a mature phenotype. Moreover, DC-targeting with fd particles double-displaying the anti-DEC-205 fragment on the pIII protein and the OVA(257-264) antigenic determinant on the pVIII protein induced potent inhibition of the growth of the B16-OVA tumor in vivo. This protection was much stronger than other immunization strategies and similar to that induced by adoptively transferred DCs. Since targeting DEC-205 in the absence of DC activation/maturation agents has previously been described to result in tolerance, the ability of fd bacteriophages to induce a strong tumor-specific immune response by targeting DCs through DEC-205 is unexpected, and further validates the potential employment of this safe, versatile and inexpensive delivery system for vaccine formulation.

Design and characterization of a peptide mimotope of the HIV-1 gp120 bridging sheet.

The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designed four linear peptide epitopes that mimic the three-dimensional structure of bridging sheet by using molecular modeling. Chemically synthesized peptides BS3 and BS4 showed a fair degree of antigenicity when tested in ELISA with IgG purified from HIV(+) broadly neutralizing sera while the production of synthetic peptides BS1 and BS2 failed due to their high degree of hydrophobicity. To overcome this limitation, we linked all four BS peptides to the COOH-terminus of GST protein to test both their antigenicity and immunogenicity. Only the BS1 peptide showed good antigenicity; however, no envelope specific antibodies were elicited upon mice immunization. Therefore we performed further analyses by linking BS1 peptide to the NH2-terminus of the E2 scaffold from the Geobacillus Stearothermophylus PDH complex. The E2-BS1 fusion peptide showed good antigenic results, however only one immunized rabbit elicited good antibody titers towards both the monomeric and oligomeric viral envelope glycoprotein (Env). In addition, moderate neutralizing antibodies response was elicited against two HIV-1 clade B and one clade C primary isolates. These preliminary data validate the peptide mimotope approach as a promising tool to obtain an effective HIV-1 vaccine.

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers.

Biomarkers (BMs) are medical signs which can be precisely measured and reproduced. Mainly, BMs provide information on the likely disease which can occur in an individual. On the other hand, BMs also signal disease recurrence in patients receiving therapy. The U.S. Food and Drug Administration coupled with the National Institutes of Health and the European Medicines Agency have proposed two distinct procedures to validate BMs. These agencies have elaborated two glossaries to describe the role of BMs. The aim of this study was to investigate medical taxonomies adopted by different governmental agencies for BM validation. Additional goals were to analyze efficiencies of the validated and candidate BMs for thyroid cancers (TCs). Currently, thyroglobulin is validated for monitoring TCs. Sorafenib-tosylate, Doxorubicin-hydrochloride, Vandetanib, Cabozantinib-s-malate, Dabrafenib-mesylate, Trametinib-dimethyl-sulfoxide, Lenvatinib-mesylate, Pralsetinib and Selpercatinib are validated for TC treatment. Among candidate BMs for TC diagnosis, there are molecular combinations including BRAF, RAS, RET/PTC and PAX8-PPARγ mutations. Noteworthy are BRAF and RET/PTC alterations already validated as targets of Dabrafenib-mesylate, Pralsetinib and Selpercatinib. Finally, cellular expressions of c-met in nodal TC metastases have diagnostic imaging applications. On the basis of this analysis, BM taxonomies should have common standards internationally recognized. BMs show different efficiencies depending on their diagnostic or therapeutic use.

Comparative analysis of the neutralizing activity against SARS-CoV-2 Wuhan-Hu-1 strain and variants of concern: Performance evaluation of a pseudovirus-based neutralization assay.

Objectives: Emergence of new variants of SARS-CoV-2 might affect vaccine efficacy. Therefore, assessing the capacity of sera to neutralize variants of concern (VOCs) in BSL-2 conditions will help evaluating the immune status of population following vaccination or infection. Methods: Pseudotyped viruses bearing SARS-CoV-2 spike protein from Wuhan-Hu-1/D614G strains (wild type, WT), B.1.617.2 (Delta), or B.1.1.529 (Omicron) VOCs were generated to assess the neutralizing antibodies (nAbs) activity by a pseudovirus-based neutralization assay (PVNA). PVNA performance was assessed in comparison to the micro-neutralization test (MNT) based on live viruses. Sera collected from COVID-19 convalescents and vaccinees receiving mRNA (BNT16b2 or mRNA-1273) or viral vector (AZD1222 or Ad26.COV2.S) vaccines were used to measure nAbs elicited by two-dose BNT16b2, mRNA-1273, AZD1222 or one-dose Ad26.CO2.S, at different times from completed vaccination, ~ 1.5 month and ~ 4-6 months. Sera from pre-pandemic and unvaccinated individuals were analyzed as controls. Neutralizing activity following booster vaccinations against VOCs was also determined. Results: PVNA titers correlated with the gold standard MNT assay, validating the reliability of PVNA. Sera analyzed late from the second dose showed a reduced neutralization activity compared to sera collected earlier. Ad26.CO2.S vaccination led to very low or absent nAbs. Neutralization of Delta and Omicron BA.1 VOCs showed significant reduction of nAbs respect to WT strain. Importantly, booster doses enhanced Omicron BA.1 nAbs, with persistent levels at 3 months from boosting. Conclusions: PVNA is a reliable tool for assessing anti-SARS-CoV-2 nAbs helping the establishment of a correlate of protection and the management of vaccination strategies.

Mesoporous Bioactive Glasses in Cancer Diagnosis and Therapy: Stimuli-Responsive, Toxicity, Immunogenicity, and Clinical Translation.

Cancer is one of the top life-threatening dangers to the human survival, accounting for over 10 million deaths per year. Bioactive glasses have developed dramatically since their discovery 50 years ago, with applications that include therapeutics as well as diagnostics. A new system within the bioactive glass family, mesoporous bioactive glasses (MBGs), has evolved into a multifunctional platform, thanks to MBGs easy-to-functionalize nature and tailorable textural properties-surface area, pore size, and pore volume. Although MBGs have yet to meet their potential in tumor treatment and imaging in practice, recently research has shed light on the distinguished MBGs capabilities as promising theranostic systems for cancer imaging and therapy. This review presents research progress in the field of MBG applications in cancer diagnosis and therapy, including synthesis of MBGs, mechanistic overview of MBGs application in tumor diagnosis and drug monitoring, applications of MBGs in cancer therapy ( particularly, targeted delivery and stimuli-responsive nanoplatforms), and immunological profile of MBG-based nanodevices in reference to the development of novel cancer therapeutics.

Exploiting viral sensing mediated by Toll-like receptors to design innovative vaccines.

Toll-like receptors (TLRs) are transmembrane proteins belonging to the family of pattern-recognition receptors. They function as sensors of invading pathogens through recognition of pathogen-associated molecular patterns. After their engagement by microbial ligands, TLRs trigger downstream signaling pathways that culminate into transcriptional upregulation of genes involved in immune defense. Here we provide an updated overview on members of the TLR family and we focus on their role in antiviral response. Understanding of innate sensing and signaling of viruses triggered by these receptors would provide useful knowledge to prompt the development of vaccines able to elicit effective and long-lasting immune responses. We describe the mechanisms developed by viral pathogens to escape from immune surveillance mediated by TLRs and finally discuss how TLR/virus interplay might be exploited to guide the design of innovative vaccine platforms.

Thyroid Stem Cells But Not Differentiated Thyrocytes Are Sensitive to Slightly Increased Concentrations of Heavy Metals.

Thyroid cancer incidence is markedly increased in volcanic areas where residents are biocontaminated by chronic lifelong exposure to slightly increased metals in the environment. Metals can influence the biology of living cells by a variety of mechanisms, depending not only on the dose and length of exposure but also on the type and stage of differentiation of target cells. We explored the effect of five heavy metals (Cu, Hg, Pd, W and Zn) at nanomolar concentrations (the biocontamination level in residents of the volcanic area in Sicily where thyroid cancer is increased) on stimulating the proliferation of undifferentiated (thyrospheres) and differentiated human thyroid cells. Thyrosphere proliferation was significantly increased after exposure to each individual metal and a greater stimulating effect was observed when a mixture of the examined metals was used. No effect was seen in differentiated thyrocytes. For all metals, the dose-response curve followed a biphasic pattern that is typical of hormesis. Thyrosphere growth concerned the size rather than number, except with the metal mixture. An altered morphology was also observed in metal-treated thyrospheres. Metal-induced proliferation was due to activation of the ERK1/2 pathway, as confirmed by growth inhibition when ERK1/2 signaling was blocked. These studies show that stem/precursor thyroid cells are sensitive to small increases in environmental metal concentrations that are harmless for differentiated thyrocytes.