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Exposure to nanoparticles is inevitable as they become widely used in industry, cosmetics, and foods. However, knowledge of their (patho)physiological effects on biological entry routes of the human body and their underlying molecular mechanisms is still fragmented. Here, we examined the molecular effects of amorphous silica nanoparticles (aSiNPs) on cell lines mimicking the alveolar-capillary barrier of the lung. After state-of-the-art characterization of the used aSiNPs and the cell model, we performed cell viability-based assays and a protein analysis to determine the aSiNP-induced cell toxicity and underlying signaling mechanisms. We revealed that aSiNPs induce apoptosis in a dose-, time-, and size-dependent manner. aSiNP-induced toxicity involves the inhibition of pro-survival pathways, such as PI3K/AKT and ERK signaling, correlating with reduced expression of the anti-apoptotic protein Survivin on the protein and transcriptional levels. Furthermore, induced Survivin overexpression mediated resistance against aSiNP-toxicity. Thus, we present the first experimental evidence suggesting Survivin as a critical cytoprotective resistor against silica-based nanotoxicity, which may also play a role in responses to other NPs. Although Survivin's relevance as a biomarker for nanotoxicity needs to be demonstrated in vivo, our data give general impetus to investigate the pharmacological modulation of Survivin's functions to attenuate the harmful effects of acute or chronic inhalative NP exposure. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with hematological diseases are particularly susceptible to COVID-19, and their vaccination has been a priority since the beginning of the pandemic. However, due to the disease itself or the treatment they receive, the protection achieved after vaccination may not be protected from severe forms of COVID-19. In this study, we analyzed the characteristics of the immune response developed by individuals with hematological cancer who received a stem cell transplant to overcome their disease after receiving the full vaccination schedule. All participants showed reduced levels of antibodies in plasma, but the cellular response of individuals with an autologous transplant was very similar to healthy donors, while it was severely impaired in individuals who received the transplant from other individuals (allogeneic). Interestingly, the transplant did not affect the immune response against SARS-CoV-2, and most infections reported after the transplant were mild, proving that some level of protection was preserved after the transplant. The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic–HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated. [ABSTRACT FROM AUTHOR]

Simple Summary: Anti-CD20 treatments produce a prolonged B-cell aplasia that is responsible for a suboptimal humoral response after vaccination against SARS-CoV-2, even months after receiving therapy. However, there is scarce information on the cellular immune response. In this study, we analyzed both cellular and humoral immune responses against SARS-CoV-2 in 18 patients treated with rituximab after receiving a COVID-19 vaccine booster dose. These studies are essential to design an efficient vaccination schedule for these individuals. Although we did not observe a significant benefit in the cellular immune response, there was an increase in the humoral response after the booster dose in rituximab-treated patients in comparison with the response after the second dose, likely due to a longer period of time since the last treatment with rituximab (9.6 versus 13.8 months, respectively). This excellent humoral response was observed even with reduced levels of total B cells, and it was likely responsible for the prevention of severe disease in individuals who acquired a breakthrough infection. The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6–9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.8 months (IQR 9.4–19) before the booster dose. One month after receiving the booster dose, the seroconversion rate in the rituximab-treated cohort increased from 83.3% to 88.9% and titers of specific IgGs against SARS-CoV-2 increased 1.53-fold (p = 0.0098), while the levels of neutralizing antibodies increased 3.03-fold (p = 0.0381). However, the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) from rituximab-treated individuals remained unchanged, and both antibody-dependent cellular cytotoxicity (ADCC) and direct cellular cytotoxicity (CDD) were reduced 1.7-fold (p = 0.0047) and 2.0-fold (p = 0.0086), respectively, in comparison with healthy donors. Breakthrough infections rate was higher in our cohort of rituximab-treated individuals (33.33%), although most of the infected patients (83.4%) developed a mild form of COVID-19. In conclusion, our findings confirm a benefit in the humoral, but not in the cellular, immune response in rituximab-treated individuals after receiving a booster dose of an mRNA-based vaccine against COVID-19. [ABSTRACT FROM AUTHOR]

Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2. Humoral response, determined by antibodies titers and neutralizing capacity, was overall impaired in individuals with OHD, except for the cohort of chronic myeloid leukemia (CML), which showed higher levels of specific IgGs than healthy donors. Conversely, the specific direct cytotoxic cellular immunity response (DCC) against SARS-CoV-2, appeared to be enhanced, especially in individuals with CML and chronic lymphocytic leukemia (CLL). This increased cellular immune response, developed earlier than in healthy donors, showed a modest cytotoxic activity that was compensated by significantly increased numbers, likely due to the disease or its treatment. The analysis of the immune response through subsequent vaccine doses will help establish the real efficacy of COVID-19 vaccines in individuals with OHD. [ABSTRACT FROM AUTHOR]

Silicon pthalocyanines (SiPcs), a class of macrocylic fused ring with 18 π-electrons system, are emerging as a wonder class of compounds in anti-cancer treatment due to their role as photosensitizers (PS) in photodynamic therapy (PDT) and as cytotoxic agent. By directing specific accumulation of SiPcs at the tumor site and initiation of destructive response only post application of irradiation of desired wavelength, a complete control over the course of treatment is achieved. Following certain modifications like incorporation of antibody drug conjugates, use of sonodynamic therapy together with PDT (SPDT) are getting introduced in this mode of treatment. They also possess appreciable topoisomerase inhibitory property and DNA intercalation property at tumor site post localization as a part of their cytotoxic response. Keeping an eye on the growing cancer burden and the advantages of SiPc derivatives, the latter may emerge as potential compounds in anti-cancer treatment in coming years. In this review article, we have summarized the reported SiPc's (2017–2021) with their mode of action. [Display omitted] • Silicon pthalocyanines (SiPcs) have superior physicochemical properties like hexacoordinated SiPc macrocyclic ring system. • Site specific localization of SiPc allows it to bypass the side effects of conventional anticancer treatment. • Attachment of axial ligands to SiPcs provide steric hindrance and good solubility profile to various organic solvents. • SiPc derivatives have provided positive results in the in silico , in vitro and in vivo studies in anticancer treatment. [ABSTRACT FROM AUTHOR]