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The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and has a complex interaction with the immune system, including growing evidence of sex-specific differences in the immune response. Sex-disaggregated analyses of epidemiological data indicate that males experience more severe symptoms and suffer higher mortality from COVID-19 than females. Many behavioural risk factors and biological factors may contribute to the different immune response. This review examines the immune response to SARS-CoV-2 infection in the context of sex, with emphasis on potential biological mechanisms explaining differences in clinical outcomes. Understanding sex differences in the pathophysiology of SARS-CoV-2 infection will help promote the development of specific strategies to manage the disease.

Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.

Recent therapeutic strategies for glioblastoma (GBM) aim at targeting immune tumor microenvironment (iTME) components to induce antitumoral immunity. A patient-tailored, ex vivo drug testing and response analysis platform for GBM would facilitate personalized therapy planning, provide insights into treatment-induced immune mechanisms in the iTME, and enable the discovery of biomarkers of therapy response and resistance.We cultured 47 GBM explants from tumor center and periphery from 7 patients in perfusion bioreactors to assess iTME responses to immunotherapy. Explants were exposed to antibodies blocking the immune checkpoints CD47, PD-1 or or their combination, and were analyzed by highly multiplexed microscopy (CODEX, co-detection by indexing) using an immune-focused 55-marker panel. Culture media were examined for changes of soluble factors including cytokines, chemokines and metabolites. CODEX enabled the spatially resolved identification and quantification of >850,000 single cells in explants, which were classified into 10 cell types by clustering. Explants from center and periphery differed significantly in their cell type composition, their levels of soluble factors, and their responses to immunotherapy. In a subset of explants, culture media displayed increased interferon-γ levels, which correlated with shifts in immune cell composition within specific tissue compartments, including the enrichment of CD4+ and CD8+ T cells within an adaptive immune compartment. Furthermore, significant differences in the expression levels of functional molecules in innate and adaptive immune cell types were found between explants responding or not to immunotherapy. In non-responder explants, T cells showed higher expression of PD-1, LAG-3, TIM-3 and VISTA, whereas in responders, macrophages and microglia showed higher cathepsin D levels. Our study demonstrates that ex vivo immunotherapy of GBM explants enables an active antitumoral immune response within the tumor center in a subset of patients, and provides a framework for multidimensional personalized assessment of tumor response to immunotherapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated symptoms, named coronavirus disease 2019 (COVID-19), have rapidly spread worldwide, resulting in the declaration of a pandemic. When several countries began enacting quarantine and lockdown policies, the pandemic as it is now known truly began. While most patients have minimal symptoms, approximately 20% of verified subjects are suffering from serious medical consequences. Co-existing diseases, such as cardiovascular disease, cancer, diabetes, and others, have been shown to make patients more vulnerable to severe outcomes from COVID-19 by modulating host–viral interactions and immune responses, causing severe infection and mortality. In this review, we outline the putative signaling pathways at the interface of COVID-19 and several diseases, emphasizing the clinical and molecular implications of concurring diseases in COVID-19 clinical outcomes. As evidence is limited on co-existing diseases and COVID-19, most findings are preliminary, and further research is required for optimal management of patients with comorbidities.

It is becoming increasingly accepted that various diseases have a capacity to alter the composition of plasma proteins. This alteration in protein composition may consequently change the targeting capacity of nanoparticles (NPs). In this study, the impact of a model targeting ligand's (i.e., Transferrin; Tf) concentration in human plasma on the targeting capacity of gold NPs (Au NPs), pre-conjugated with Tf, is investigated. Our findings demonstrate that the protein corona formation by both healthy and Tf depleted human plasma diminishes the targeting efficacy of Au NPs within human cancer cells despite a preservation of targeting ability by plasma with excess Tf (10-fold). Moreover, the plasma samples obtained from patients with various Tf levels (e.g., thalassemia major, sickle cell anemia, aplastic anemia, and iron deficiency anemia) have affected the accessibility of the targeting Tf in the corona layer and subsequently affected their targeting ability, which emphasizes the critical role of disease-specific protein corona on the efficacy of Au NPs. Ultimately, variations of protein concentration (e.g., due to disease occurrence and progress) in plasma affect its recruiting in corona formation, and in turn, affect the targeting and therapeutic efficacies of Au NPs.

Purpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. Experimental design: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.

Questions and concerns regarding the efficacy and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines have plagued scientists since the BNT162b2 mRNA vaccine was introduced in late 2020. As a result, decisions about vaccine boosters based on breakthrough infection rates and the decline of antibody titers have commanded worldwide attention and research. COVID-19 patients have displayed continued severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike-protein-specific antibodies and neutralizing antibodies in longitudinal studies; in addition, cytokine activation has been detected at early steps following SARS-CoV-2 infection. Epitopes that are highly reactive and can mediate long-term antibody responses have been identified at the spike and ORF1ab proteins. The N-terminal domain of the S1 and S2 subunits is the location of important SARS-CoV-2 spike protein epitopes. High sequence identity between earlier and newer variants of SARS-CoV-2 and different degrees of sequence homology among endemic human coronaviruses have been observed. Understanding the extent and duration of protective immunity is consequential for determining the course of the COVID-19 pandemic. Further knowledge of memory responses to different variants of SARS-CoV-2 is needed to improve the design of the vaccine.

Tumor-associated microglia (MG) and macrophages (MΦ) are important components of the glioblastoma (GBM) immune tumor microenvironment (iTME). From the recent advances in understanding how MG and GBM cells evolve and interact during tumorigenesis, we emphasize the cooperation of MG with other immune cell types of the GBM-iTME, mainly MΦ and T cells. We provide a comprehensive overview of current immunotherapeutic clinical trials and approaches for the treatment of GBM, which in general, underestimate the counteracting contribution of immunosuppressive MG as a main factor for treatment failure. Furthermore, we summarize new developments and strategies in MG reprogramming/re-education in the GBM context, with a focus on ways to boost MG-mediated tumor cell phagocytosis and associated experimental models and methods. This ultimately converges in our proposal of novel combinatorial regimens that locally modulate MG as a central paradigm, and therefore may lead to additional, long-lasting, and effective tumoricidal responses.

Macrophages are a critical member of the innate immune system and can intensify tumor invasiveness and assist the growth of neoplastic cells. Moreover, they have the capability to reinforce immunosuppression and angiogenesis. Various investigations suggest that health-related issues, including inflammatory disorders and neoplastic diseases may be caused by environmental toxicant exposure. However, it is still unclear what role these environmental toxicants play in causing carcinogenesis by disturbing the mechanisms of migration, polarization, differentiation, and immune-stimulatory functions of macrophages. Accordingly, in this article, we will explore the interaction between environmental chemicals and inflammatory macrophage processes at the molecular level and their association with tumor progression and carcinogenesis.

A significant cause of worldwide morbidity and mortality that carries a heavy health care burden is cardiovascular disease. The mortality rate of cardiovascular disease, which is considered the leading cause of death in the United States, is close to 801,000 people every year. Coronary heart disease, deep vein thrombosis, myocardial infarction (MI), and pulmonary embolism are some of the many examples of cardiovascular diseases. They all lead to ischemia and tissue death. Among them, important conditions that cause mortality are MI and heart failure. Technological innovations and novel therapies are necessary to counter these diseases given the bleak outcomes. Advances in research tools and treatments can be achieved through the synergy of biology and nanotechnology. Nanoparticles (NPs) for drug delivery and therapeutic stem cells (SCs) are specific examples of nanobiotechnology in action. Aside from drug delivery, nanotechnology can be utilized for other therapeutic purposes in treating cardiovascular diseases. SC therapy, which has the capacity to improve repair of cardiac tissue, is an example.

Nanotechnology has garnered tremendous interest from the scientific community and captured the vivid imagination of the general public for many years. It is a broad field of study that spans various scientific disciplines with myriad useful applications. In medicine, nanotechnology is being developed for a multitude of purposes to improve the diagnosis, management, and treatment of diseases. This chapter provides a brief historical timeline of nanotechnology and nanomedicine, describes the current state of nanomedicine, and lays the basic groundwork for further discussions about nanotechnology in cardiology.

There is an increasing body of evidence demonstrating the importance of paracrine factors in a wide range of diseases. Paracrine factors such as growth factors and cytokines are soluble signaling proteins synthesized and secreted by cells and can diffuse over short distances to induce changes in neighboring cells. They act locally and show short and slow diffusion in the extracellular matrix to interact with their receptors to activate signaling pathways that control a variety of cellular processes such as proliferation, survival, migration, and differentiation. This chapter provides the latest advances in the development of different nanoparticulate systems for the delivery of paracrine factors to increase availability, preserve bioactivity, functionality and stability, and control release of paracrine factors to the region of interest.

Cardiovascular diseases (CVDs), including heart failure, myocardial infarction, coronary artery disease, and inflammatory heart disease, offer as one of the biggest health challenges around the world. Unfortunately, because of a growth in the risk factors of CVD, such as obesity and diabetes, it is expected that in next 10 years there will be raise in CVDs. Despite promising improvements in therapeutic modalities and pharmacological progressions, the discovery of innovative and more effective therapies is still essentially needed. Nanomedicine has become one of the interesting areas of research that is expected to fill this gap through the development of CVD care system.

When the heart can no longer meet the body’s demands by providing sufficient blood pressure and/or flow, heart failure arises. The body responds to this failure, such as releasing neurohormones that stimulate the organs, retaining salt and water by the kidneys, and changing cellular and organ structure and function by activating intracellular signaling pathways in the vasculature and heart. At first, lower cardiac performance can be counteracted by these “compensatory” responses. However, these responses eventually contribute to disease progression by raising the probability of organ failure and exacerbating clinical prognosis. Heart failure may present with many variations in clinical presentation, but some symptoms are common, such as fatigue, fluid retention, and shortness of breath. Systolic heart failure (dilated heart and contractile failure) occurs in approximately 50% of all people. Diastolic heart failure (heart failure with a preserved ejection fraction (HFpEF)) comprises the other 50% and usually presents with a hypertrophied, nondilated heart which contracts normally. There is a rise in the worldwide prevalence of HFpEF, but the condition has not been well-investigated.

A considerable increase in research using nanotechnology for biomedical applications including diagnostics, drug delivery systems, imaging agents, implant coatings, and other therapeutic techniques has occurred since the beginning of this century. The ability of nanoparticles (NPs) to mediate biological effects due to their distinctive physico-chemical properties makes them attractive in medicine and nanomedicine (e.g., increase in implant performance by nano-textured surfaces, improvement in NP delivery of therapeutics into tumors by the enhanced permeability and retention (EPR) effect, enhancement of MRI contrast by superparamagnetic NPs). In addition, commercialization of technology is another unique benefit of NPs (e.g., rediscovery of drugs that may have been clinically unsuccessful in the past, give greater intellectual property protection, allow novel drug indications).

The adult myocardium has a limited regenerative capacity following heart injury and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF post-myocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nano-bioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.