Immune Evasion Properties Research Articles

Stemness in solid malignancies: coping with immune attack.

Immunotherapy has become a key new pillar of cancer treatment, and this has sparked interest in understanding mechanisms of cancer immune evasion. It has long been appreciated that cancers are constituted by heterogeneous populations of tumour cells. This feature is often fuelled by specialized cells that have molecular programs resembling tissue stem cells. Although these cancer stem cells (CSCs) have capacity for unlimited self-renewal and differentiation, it is increasingly evident that some CSCs are capable of achieving remarkable immune resistance. Given that most immunotherapy regiments have overlooked CSC-specific immune-evasive mechanisms, many current treatment strategies often lead to cancer relapse. This Review focuses on advancements in understanding how CSCs in solid tumours achieve their unique immune-evasive properties, enabling them to drive tumour regrowth. Moreover, as cancers often arise from tissue stem cells that acquired oncogenic mutations, we discuss how tissue stem cells undergoing malignant transformation activate intrinsic immune-evasive mechanisms and establish close interactions with suppressive immune cells to escape immune surveillance. In addition, we summarize how in advanced disease stages, CSCs often hijack features of normal stem cells to resist antitumour immunity. Finally, we provide insights in how to design a new generation of cancer immunotherapies to ensure elimination of CSCs.

Analysis of the impact of coronavirus infection on human health: epidemiological data, vaccination strategies, psychological aspect, consequences (literature review)

The COVID-19 (COronaVIrus Disease 2019) pandemic has caused widespread morbidity, mortality, and socioeconomic crisis around the world. Since its first outbreak in 2019, COVID-19 has evolved continuously, leading to the emergence of several variants that have gained greater transmission efficiency, severity, and immune evasion properties. Vaccination has proven to be an important strategy to control the spread of the virus and mitigate its impact. The development of multiple COVID-19 vaccines within 1 year of the virus's emergence was unprecedented. The purpose of the article was to analyze and summarize the scientific literature on the impact of COVID-19 on global health, including epidemiological data, vaccination strategies, psychological impact of the pandemic, and human health outcomes. The analysis found that COVID-19 vaccination has been very effective in reducing morbidity, hospitalizations and intensive care unit admissions. However, ongoing surveillance, monitoring of options and adaptive vaccination strategies are crucial to maximize the benefits of vaccination and effectively control the spread of the virus. Globally, the dramatic and rapid spread of COVID-19 has triggered social changes that have led to an increased burden of mental health and fear-related behaviors. The physical and social distancing imposed in many parts of the world has had a significant impact on how the general population communicates and interacts with each other. Extreme avoidance of the lack of social contact has created a sense of "disconnection" that has been further exacerbated by the inability to meet friends and family at social gatherings and supportive places such as churches, restaurants, workplaces, and sports facilities. The closure of schools and many businesses, along with rising unemployment, further exacerbated feelings of isolation, financial hardship, anxiety, and depression. The article provides information on the mental impact of COVID-19 on patients, namely, the virus contributes to mental distress, anxiety, depression, suicide risk, post-traumatic stress disorder, cognitive impairment and sleep disorders. Keywords: COVID, spread, vaccines, anxiety, depression.

A Quadruple Gene-Deleted Live BoHV-1 Subunit RVFV Vaccine Vector Reactivates from Latency and Replicates in the TG Neurons of Calves but Is Not Transported to and Shed from Nasal Mucosa.

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV.

Structure of anellovirus-like particles reveal a mechanism for immune evasion

Anelloviruses are nonpathogenic viruses that comprise a major portion of the human virome. Despite being ubiquitous in the human population, anelloviruses (ANVs) remain poorly understood. Basic features of the virus, such as the identity of its capsid protein and the structure of the viral particle, have been unclear until now. Here, we use cryogenic electron microscopy to describe the first structure of an ANV-like particle. The particle, formed by 60 jelly roll domain-containing ANV capsid proteins, forms an icosahedral particle core from which spike domains extend to form a salient part of the particle surface. The spike domains come together around the 5-fold symmetry axis to form crown-like features. The base of the spike domain, the P1 subdomain, shares some sequence conservation between ANV strains while a hypervariable region, forming the P2 subdomain, is at the spike domain apex. We propose that this structure renders the particle less susceptible to antibody neutralization by hiding vulnerable conserved domains while exposing highly diverse epitopes as immunological decoys, thereby contributing to the immune evasion properties of anelloviruses. These results shed light on the structure of anelloviruses and provide a framework to understand their interactions with the immune system.

The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells

ObjectivePancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant ‘stem-like’ cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending...

Tracking the Spread of the BA.2.86 Lineage in Italy Through Wastewater Analysis

The emergence of new SARS-CoV-2 variants poses challenges to global surveillance efforts, necessitating swift actions in their detection, evaluation, and management. Among the most recent variants, Omicron BA.2.86 and its sub-lineages have gained attention due to their potential immune evasion properties. This study describes the development of a digital PCR assay for the rapid detection of BA.2.86 and its descendant lineages, in wastewater samples. By using this assay, we analyzed wastewater samples collected in Italy from September 2023 to January 2024. Our analysis revealed the presence of BA.2.86 lineages already in October 2023 with a minimal detection rate of 2% which then rapidly increased, becoming dominant by January 2024, accounting for a prevalence of 62%. The findings emphasize the significance of wastewater-based surveillance in tracking emerging variants and underscore the efficacy of targeted digital PCR assays for environmental monitoring.

Beyond the double helix: the multifaceted landscape of extracellular DNA in Staphylococcus aureus biofilms.

Staphylococcus aureus forms biofilms consisting of cells embedded in a matrix made of proteins, polysaccharides, lipids, and extracellular DNA (eDNA). Biofilm-associated infections are difficult to treat and can promote antibiotic resistance, resulting in negative healthcare outcomes. eDNA within the matrix contributes to the stability, growth, and immune-evasive properties of S. aureus biofilms. eDNA is released by autolysis, which is mediated by murein hydrolases that access the cell wall via membrane pores formed by holin-like proteins. The eDNA content of S. aureus biofilms varies among individual strains and is influenced by environmental conditions, including the presence of antibiotics. eDNA plays an important role in biofilm development and structure by acting as an electrostatic net that facilitates protein-cell and cell-cell interactions. Because of eDNA's structural importance in biofilms and its ubiquitous presence among S. aureus isolates, it is a potential target for therapeutics. Treatment of biofilms with DNase can eradicate or drastically reduce them in size. Additionally, antibodies that target DNABII proteins, which bind to and stabilize eDNA, can also disperse biofilms. This review discusses the recent literature on the release, structure, and function of eDNA in S. aureus biofilms, in addition to a discussion of potential avenues for targeting eDNA for biofilm eradication.

Analysis of the impact of pluronic acid on the thermal stability and infectivity of AAV6.2FF

BackgroundThe advancement of AAV vectors into clinical testing has accelerated rapidly over the past two decades. While many of the AAV vectors being utilized in clinical trials are derived from natural serotypes, engineered serotypes are progressing toward clinical translation due to their enhanced tissue tropism and immune evasive properties. However, novel AAV vectors require formulation and stability testing to determine optimal storage conditions prior to their use in a clinical setting.ResultsHere, we evaluated the thermal stability of AAV6.2FF, a rationally engineered capsid with strong tropism for lung and muscle, in two different buffer formulations; phosphate buffered saline (PBS), or PBS supplemented with 0.001% non-ionic surfactant Pluronic F68 (PF-68). Aliquots of AAV6.2FF vector encoding the firefly luciferase reporter gene (AAV6.2FF-ffLuc) were incubated at temperatures ranging from -20°C to 55°C for varying periods of time and the impact on infectivity and particle integrity evaluated. Additionally, the impact of several rounds of freeze-thaw treatments on the infectivity of AAV6.2FF was investigated. Vector infectivity was measured by quantifying firefly luciferase expression in HEK 293 cells and AAV particle integrity was measured by qPCR quantification of encapsidated viral DNA.ConclusionsOur data demonstrate that formulating AAV6.2FF in PBS containing 0.001% PF-68 leads to increased stability and particle integrity at temperatures between -20℃ to 21℃ and protection against the destructive effects of freeze-thaw. Finally, AAV6.2FF-GFP formulated in PBS supplemented with 0.001% PF-68 displayed higher transduction efficiency in vivo in murine lung epithelial cells following intranasal administration than vector buffered in PBS alone further demonstrating the beneficial properties of PF-68.

Engineering immune-evasive allogeneic cellular immunotherapies.

Allogeneic cellular immunotherapies hold a great promise for cancer treatment owing to their potential cost-effectiveness, scalability and on-demand availability. However, immune rejection of adoptively transferred allogeneic T and natural killer (NK) cells is a substantial obstacle to achieving clinical responses that are comparable to responses obtained with current autologous chimeric antigen receptor T cell therapies. In this Perspective, we discuss strategies to confer cell-intrinsic, immune-evasive properties to allogeneic T cellsand NK cells in order to prevent or delay their immune rejection, thereby widening the therapeutic window. We discuss how common viral and cancer immune escape mechanisms can serve as a blueprint for improving the persistence of off-the-shelf allogeneic cell therapies. The prospects of harnessing genome editing and synthetic biology to design cell-based precision immunotherapies extend beyond programming target specificities and require careful consideration of innate and adaptive responses in the recipient that may curtail the biodistribution, in vivo expansion and persistence of cellular therapeutics.

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma

Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944–5p, miR-105–5p, miR-486–5p, miR-506–5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs—CCAT-1, MALAT-1, or H19—markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486–5p, miR-506–5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944–5p and miR-105–5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105–5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105–5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.

Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicate in IGROV-1 but no longer in Vero E6 and are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals are markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhances NAb responses against both XBB and BA.2.86 variants. JN.1 displays lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.

AlphaFold2-Enabled Atomistic Modeling of Structure, Conformational Ensembles, and Binding Energetics of the SARS-CoV-2 Omicron BA.2.86 Spike Protein with ACE2 Host Receptor and Antibodies: Compensatory Functional Effects of Binding Hotspots in Modulating Mechanisms of Receptor Binding and Immune Escape.

The latest wave of SARS-CoV-2 Omicron variants displayed a growth advantage and increased viral fitness through convergent evolution of functional hotspots that work synchronously to balance fitness requirements for productive receptor binding and efficient immune evasion. In this study, we combined AlphaFold2-based structural modeling approaches with atomistic simulations and mutational profiling of binding energetics and stability for prediction and comprehensive analysis of the structure, dynamics, and binding of the SARS-CoV-2 Omicron BA.2.86 spike variant with ACE2 host receptor and distinct classes of antibodies. We adapted several AlphaFold2 approaches to predict both the structure and conformational ensembles of the Omicron BA.2.86 spike protein in the complex with the host receptor. The results showed that the AlphaFold2-predicted structural ensemble of the BA.2.86 spike protein complex with ACE2 can accurately capture the main conformational states of the Omicron variant. Complementary to AlphaFold2 structural predictions, microsecond molecular dynamics simulations reveal the details of the conformational landscape and produced equilibrium ensembles of the BA.2.86 structures that are used to perform mutational scanning of spike residues and characterize structural stability and binding energy hotspots. The ensemble-based mutational profiling of the receptor binding domain residues in the BA.2 and BA.2.86 spike complexes with ACE2 revealed a group of conserved hydrophobic hotspots and critical variant-specific contributions of the BA.2.86 convergent mutational hotspots R403K, F486P, and R493Q. To examine the immune evasion properties of BA.2.86 in atomistic detail, we performed structure-based mutational profiling of the spike protein binding interfaces with distinct classes of antibodies that displayed significantly reduced neutralization against the BA.2.86 variant. The results revealed the molecular basis of compensatory functional effects of the binding hotspots, showing that BA.2.86 lineage may have evolved to outcompete other Omicron subvariants by improving immune evasion while preserving binding affinity with ACE2 via through a compensatory effect of R493Q and F486P convergent mutational hotspots. This study demonstrated that an integrative approach combining AlphaFold2 predictions with complementary atomistic molecular dynamics simulations and robust ensemble-based mutational profiling of spike residues can enable accurate and comprehensive characterization of structure, dynamics, and binding mechanisms of newly emerging Omicron variants.

Prototype and BA.5 protein nanoparticle vaccines protect against Omicron BA.5 variant in Syrian hamsters.

As SARS-CoV-2 continues to evolve, there may be a need to update the vaccines to match the newly emerging variants. Here, we compared the protective efficacy of the updated BA.5 and the original Wuhan-1 COVID-19 vaccine against a challenge with the BA.5 Omicron variant of SARS-CoV-2 in hamsters. Both vaccines induced similar levels of neutralizing antibodies against multiple variants of SARS-CoV-2. One and three months after the final immunization, hamsters were challenged with BA.5. No differences in protection against the BA.5 variant virus were observed between the two vaccines, although fewer breakthrough infections were detected in the BA.5-vaccinated hamsters. Together, our data show that both protein nanoparticle vaccines are effective against the BA.5 variant of SARS-CoV-2 but given the increased number of breakthrough infections and continued evolution, it is important to update the COVID-19 vaccine for long-term protection.

HCV-induced autophagy and innate immunity.

The interplay between autophagy and host innate immunity has been of great interest. Hepatitis C virus (HCV) impedes signaling pathways initiated by pattern-recognition receptors (PRRs) that recognize pathogens-associated molecular patterns (PAMPs). Autophagy, a cellular catabolic process, delivers damaged organelles and protein aggregates to lysosomes for degradation and recycling. Autophagy is also an innate immune response of cells to trap pathogens in membrane vesicles for removal. However, HCV controls the autophagic pathway and uses autophagic membranes to enhance its replication. Mitophagy, a selective autophagy targeting mitochondria, alters the dynamics and metabolism of mitochondria, which play important roles in host antiviral responses. HCV also alters mitochondrial dynamics and promotes mitophagy to prevent premature cell death and attenuate the interferon (IFN) response. In addition, the dysregulation of the inflammasomal response by HCV leads to IFN resistance and immune tolerance. These immune evasion properties of HCV allow HCV to successfully replicate and persist in its host cells. In this article, we discuss HCV-induced autophagy/mitophagy and its associated immunological responses and provide a review of our current understanding of how these processes are regulated in HCV-infected cells.

Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants

The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.

Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.

Characterization of a SARS-CoV-2 EG.5.1 clinical isolate in vitro and in vivo

EG.5.1 is a subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB variant that is rapidly increasing in prevalence worldwide. However, the pathogenicity, transmissibility, and immune evasion properties of isolates of EG.5.1 are largely unknown. Here, we show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5 in hamsters. We also demonstrate that, like XBB.1.5, EG.5.1 is transmitted more efficiently between hamsters compared to its predecessor, BA.2. In contrast, unlike XBB.1.5, we detect EG.5.1 in the lungs of four of six exposed hamsters, suggesting that the virus properties of EG.5.1 are different from those of XBB.1.5. Finally, we find that the neutralizing activity of plasma from convalescent individuals against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. Our data suggest that the different virus properties after transmission and the altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in humans.

Abstract 16213: No Cardiac Benefit After Single Dose of Intramyocardial or Intravenous Mesenchymal Stem Cell-Derived Extracellular Vesicles Post-Myocardial Infarction Supports Need for Bioengineered Extracellular Vesicles With Non-Invasive Cardiac Uptake

Introduction: In pre-clinical models, mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have benefits in ischemic CVD. We previously showed that only intramyocardial (IM) injection of MSC-EV, an invasive method of administration, and not intravenous (IV) injection, resulted in reliable cardiac uptake after acute MI. No prior studies have compared the functional outcome of IM versus IV injection after acute MI. Hypothesis: IM injection of MSC-EV will result in improved cardiac outcomes whereas IV injection will not. Aim: To demonstrate the long-term outcomes of IM versus IV MSC-EV after acute MI. Methods: MSC-EV were isolated and characterized. FVB mice underwent left anterior descending coronary artery ligation and subsequent injection of the following: 1) IM saline control (IM-C; n = 8), 2) IM 2*10 9 MSC-EV particles (IM-EV; n = 9), 3) IV saline control (IV-C; n = 8), and 4) IV 2*10 9 MSC-EV particles (IV-EV; n = 8). The mice underwent pre-operative, and post-operative weekly echocardiograms. On post-operative day 28, the mice were euthanized, and the hearts were harvested. Results: Preliminary data showed no significant differences in left ventricular ejection fraction (p = 0.6151) or fractional shortening (p = 0.1135) in the IM-EV and IV-EV groups compared to the controls IM-C and IV-C, respectively, at post-operative day 28 (Figure 1A). There were also no significant differences in infarct size (p = 0.05620) (Figure 1B) or anterior border zone fibrosis (p = 0.6333) (Figure 1C) on Masson-Trichrome staining. Conclusions: Preliminary findings demonstrate that a one-time IM or IV dose of MSC-EV given immediately after acute MI results in no observable effects. Additional MSC-EV doses after MI may produce beneficial effects. Results from our ongoing studies on the creation of stem cells bioengineered to produce MSC-EV with surface cardiac targeting peptides and immune-evasion properties will be presented in August 2023.

Cancer Cell Membrane-Based Materials for Biomedical Applications.

The nanodelivery system provides a novel direction for disease diagnosis and treatment; however, its delivery effectiveness is restricted by the short biological half-life and inadequate tumor targeting. The immune evasion properties and homologous targeting capabilities of natural cell membranes, particularly those of cancer cell membranes (CCM), have gained significant interest. The integration of CCM and nanoparticles has resulted in the emergence of CCM-based nanoplatforms (CCM-NPs), which have gained significant attention due to their unique properties. CCM-NPs not only prolong the blood circulation time of core nanoparticles, but also direct them for homologous tumor targeting. Herein, the history and development of CCM-NPs as well as how these platforms have been used for biomedical applications are discussed. The application of CCM-NPs for cancer therapy will be described in detail. Translational efforts are currently under way and further research to address key areas of need will ultimately be required to facilitate the successful clinical adoption of CCM-NPs.

From Alpha to Omicron: How Different Variants of Concern of the SARS-Coronavirus-2 Impacted the World.

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and the generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting in the emergence of several lineages and variants of concern (VOC) that have gained more efficient transmission, severity, and immune evasion properties. The World Health Organization has given these variants names according to the letters of the Greek Alphabet, starting with the Alpha (B.1.1.7) variant, which emerged in 2020, followed by the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. This review explores the genetic variation among different VOCs of SARS-CoV-2 and how the emergence of variants made a global impact on the pandemic.