Self-adhesive hydrogel meshes reduce tissue incorporation and mechanical behavior versus microgrips self-fixation: a preclinical study

Purpose Atraumatic mesh fixation for abdominal hernia repair has been developed to avoid the disadvantages of classical fixation with sutures, which is considered a cause of chronic pain and discomfort. This study was designed to analyze, in the short and medium term, the biological and mechanical behavior of two self-fixing meshes compared to that of a polypropylene (PP) mesh fixed with a cyanoacrylate (CA) tissue adhesive. Methods Partial abdominal wall defects (6 × 4 cm) were created in New Zealand rabbits (n = 36) and repaired using a self-adhesive hydrogel mesh (Adhesix™), a self-gripping mesh (ProGrip™) or a PP mesh fixed with CA (Surgipro™ CA). After 14 and 90 days, the host tissue incorporation, macrophage response and biomechanical strength were examined. Results At 14 and 90 days, the ProGrip and Surgipro CA meshes showed good host tissue incorporation; however, the Adhesix implants presented poor integration, seroma formation and a higher degree of shrinkage. The Adhesix hydrogel was completely reabsorbed at 14 days, whereas ProGrip microhooks were observed at all study times. The macrophage response was higher in the ProGrip and Surgipro CA groups at 14 and 90 days, respectively, and decreased over time. At 90 days, the ProGrip implants showed the highest tensile strength values and the Adhesix implants showed the highest failure stretch. Conclusion Meshes with mechanical microgrip self-fixation (ProGrip) show better biological and mechanical behavior than those with adhesive hydrogel (Adhesix) in a preclinical model of abdominal hernia repair in rabbits.

Slow expanders invade by forming dented fronts in microbial colonies

Most organisms grow in space, whether they are viruses spreading within a host tissue or invasive species colonizing a new continent. Evolution typically selects for higher expansion rates during spatial growth, but it has been suggested that slower expanders can take over under certain conditions. Here, we report an experimental observation of such population dynamics. We demonstrate that mutants that grow slower in isolation nevertheless win in competition, not only when the two types are intermixed, but also when they are spatially segregated into sectors. The latter was thought to be impossible because previous studies focused exclusively on the global competitions mediated by expansion velocities, but overlooked the local competitions at sector boundaries. Local competition, however, can enhance the velocity of either type at the sector boundary and thus alter expansion dynamics. We developed a theory that accounts for both local and global competitions and describes all possible sector shapes. In particular, the theory predicted that a slower on its own, but more competitive, mutant forms a dented V-shaped sector as it takes over the expansion front. Such sectors were indeed observed experimentally, and their shapes matched quantitatively with the theory. In simulations, we further explored several mechanisms that could provide slow expanders with a local competitive advantage and showed that they are all well-described by our theory. Taken together, our results shed light on previously unexplored outcomes of spatial competition and establish a universal framework to understand evolutionary and ecological dynamics in expanding populations.

The Remarkable Evolutionary Plasticity of Coronaviruses by Mutation and Recombination: Insights for the COVID-19 Pandemic and the Future Evolutionary Paths of SARS-CoV-2

Coronaviruses (CoVs) constitute a large and diverse subfamily of positive-sense single-stranded RNA viruses. They are found in many mammals and birds and have great importance for the health of humans and farm animals. The current SARS-CoV-2 pandemic, as well as many previous epidemics in humans that were of zoonotic origin, highlights the importance of studying the evolution of the entire CoV subfamily in order to understand how novel strains emerge and which molecular processes affect their adaptation, transmissibility, host/tissue tropism, and patho non-homologous genicity. In this review, we focus on studies over the last two years that reveal the impact of point mutations, insertions/deletions, and intratypic/intertypic homologous and non-homologous recombination events on the evolution of CoVs. We discuss whether the next generations of CoV vaccines should be directed against other CoV proteins in addition to or instead of spike. Based on the observed patterns of molecular evolution for the entire subfamily, we discuss five scenarios for the future evolutionary path of SARS-CoV-2 and the COVID-19 pandemic. Finally, within this evolutionary context, we discuss the recently emerged Omicron (B.1.1.529) VoC.

Bletilla striata polysaccharide cryogel scaffold for spatial control of foreign-body reaction

Background Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants. Methods First, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials. Results Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure. Conclusions Collectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.

Developmental Aspects of SARS-CoV-2, Potential Role of Exosomes and Their Impact on the Human Transcriptome

With over 4.8 million deaths within 2 years, time is of the essence in combating COVID-19. The infection now shows devastating impacts on the younger population, who were not previously predicted to be vulnerable, such as in the older population. COVID-19-related complications have been reported in neonates whose mothers were infected with SARS-CoV-2 during pregnancy, and in children who get infected. Hence, a deeper understanding of the pathophysiology of COVID-19 during various developmental stages and placental transmission is essential. Although a connection has not yet been established between exosomal trafficking and the placental transmission of COVID-19, reports indicate that SARS-CoV-2 components may be trafficked between cells through exosomes. As the infection spreads, the transcriptome of cells is drastically perturbed, e.g., through the severe upregulation of several immune-related genes. Consequently, a major outcome of COVID-19 is an elevated immune response and the detection of viral RNA transcripts in host tissue. In this direction, this review focuses on SARS-CoV-2 virology, its in utero transmission from infected pregnant mothers to fetuses, SARS-CoV-2 and exosomal cellular trafficking, transcriptomic impacts, and RNA-mediated therapeutics against COVID-19. Future research will establish stronger connections between the above processes to develop diagnostic and therapeutic solutions towards COVID-19 and similar viral outbreaks.

Possible impacts of the predominant Bacillus bacteria on the Ophiocordyceps unilateralis s. l. in its infected ant cadavers

Animal hosts infected and killed by parasitoid fungi become nutrient-rich cadavers for saprophytes. Bacteria adapted to colonization of parasitoid fungi can be selected and can predominate in the cadavers, actions that consequently impact the fitness of the parasitoid fungi. In Taiwan, the zombie fungus, Ophiocordyceps unilateralis sensu lato (Clavicipitaceae: Hypocreales), was found to parasitize eight ant species, with preference for a principal host, Polyrhachis moesta. In this study, ant cadavers grew a fungal stroma that was predominated by Bacillus cereus/thuringiensis. The bacterial diversity in the principal ant host was found to be lower than the bacterial diversity in alternative hosts, a situation that might enhance the impact of B. cereus/thuringiensis on the sympatric fungus. The B. cereus/thuringiensis isolates from fungal stroma displayed higher resistance to a specific naphthoquinone (plumbagin) than sympatric bacteria from the environment. Naphthoquinones are known to be produced by O. unilateralis s. l., and hence the resistance displayed by B. cereus/thuringiensis isolates to these compounds suggests an advantage to B. cereus/thuringiensis to grow in the ant cadaver. Bacteria proliferating in the ant cadaver inevitably compete for resources with the fungus. However, the B. cereus/thuringiensis isolates displayed in vitro capabilities of hemolysis, production of hydrolytic enzymes, and antagonistic effects to co-cultured nematodes and entomopathogenic fungi. Thus, co-infection with B. cereus/thuringiensis offers potential benefits to the zombie fungus in killing the host under favorable conditions for reproduction, digesting the host tissue, and protecting the cadaver from being taken over by other consumers. With these potential benefits, the synergistic effect of B. cereus/thuringiensis on O. unilateralis infection is noteworthy given the competitive relationship of these two organisms sharing the same resource.

The Influence of Symbiont Diversity on the Functional Biology of a Model Sea Anemone

<p>Cnidarian–dinoflagellate symbioses, particularly those between anthozoans and dinoflagellates of the genus Symbiodinium (commonly referred to as zooxanthellae) are widespread in the marine environment. They are responsible for the formation of coral reefs and are thus of great ecological importance. In recent years there has been an increase in the frequency and severity of episodes of coral bleaching resulting in degradation and mortality of coral reefs on a global scale. In order to gain a deeper understanding of how corals can adapt to changing environmental conditions, the effect that symbiont type has on the persistence and physiology of an association needs to be ascertained. The aim of this research was to determine how different symbiont types affect the nutritional biology and intracellular physiology of the symbiosis when in association with the sea anemone Aiptasia pulchella. The specific objectives of the study were to; (1) determine whether different symbiont types are equally as adept at supporting the energetic demands of the same host; (2) determine if internal pH (pHi) is a reflection of symbiont type and whether the optimal pH for photosynthesis coincides with the host cell pHi; and (3) test the influence of Symbiodinium type on host tissue glycerol and glucose pools. In order to answer these questions, aposymbiotic (i.e. symbiont-free) sea anemones were infected with different Symbiodinium types and the relationship between symbiont type, photosynthetic performance and autotrophic potential was tested. A range of ‘normal’ and novel cnidarian–dinoflagellate symbioses was also used to measure host cell pHi and to determine the optimal pHi of isolated intact symbiosomes (i.e. the vacuoles that house the symbionts), as well as to compare the amounts of free glycerol and glucose (metabolites) present in the host tissues. Different host-symbiont combinations were found to have different photosynthetic and respiratory attributes. Earlier onset of full autotrophy (i.e. when all metabolic carbon demands of the symbiosis were met by photosynthesis) and higher CZAR values (i.e. the contribution of zooxanthellae to animal respiration) were demonstrated by symbioses hosting Symbiodinium B1 both from the original (homologous) and different (heterologous) host. The study showed that Symbiodinium types differ in their pH optima and that the optimal pHi for photosynthesis does not always match the actual measured pHi. Symbiont type was also shown to have an effect on host tissue glycerol and glucose pools, with the associations harbouring the homologous Symbiodinium B1 attaining the highest concentrations of both metabolites. Findings from this study suggest that corals may be able to maintain an association with a range of Symbiodinium types, and hence potentially switch as a consequence of bleaching. The new symbiont type may not be as nutritionally advantageous as the original type however, which could have implications for the growth and survivorship of the coral, unless it is able to supplement its carbon demands heterotrophically. The rapid proliferation of some of the heterologous Symbiodinium types (e.g. Symbiodinium E2) inside the host indicates that, after bleaching, there is potential for fast symbiont establishment. The reduced carbon contribution of these heterologous symbionts may not be a major concern should the coral be able to reinstate the more nutritionally advantageous symbiont as the dominant type during bleaching recovery. Finally, the rapid proliferation demonstrated by the heterologous Symbiodinium types and the associated metabolic cost to the host, could be an indication of the opportunistic nature of some of these types and may indicate a shift towards parasitism. It is imperative to extend this type of work to corals in the field to determine how these associations behave in nature. Also, in order to get a clearer picture of the diversity in symbiosis physiology, a wider range of Symbiodinium types needs to be investigated.</p>

The Influence of Symbiont Diversity on the Functional Biology of a Model Sea Anemone

<p>Cnidarian–dinoflagellate symbioses, particularly those between anthozoans and dinoflagellates of the genus Symbiodinium (commonly referred to as zooxanthellae) are widespread in the marine environment. They are responsible for the formation of coral reefs and are thus of great ecological importance. In recent years there has been an increase in the frequency and severity of episodes of coral bleaching resulting in degradation and mortality of coral reefs on a global scale. In order to gain a deeper understanding of how corals can adapt to changing environmental conditions, the effect that symbiont type has on the persistence and physiology of an association needs to be ascertained. The aim of this research was to determine how different symbiont types affect the nutritional biology and intracellular physiology of the symbiosis when in association with the sea anemone Aiptasia pulchella. The specific objectives of the study were to; (1) determine whether different symbiont types are equally as adept at supporting the energetic demands of the same host; (2) determine if internal pH (pHi) is a reflection of symbiont type and whether the optimal pH for photosynthesis coincides with the host cell pHi; and (3) test the influence of Symbiodinium type on host tissue glycerol and glucose pools. In order to answer these questions, aposymbiotic (i.e. symbiont-free) sea anemones were infected with different Symbiodinium types and the relationship between symbiont type, photosynthetic performance and autotrophic potential was tested. A range of ‘normal’ and novel cnidarian–dinoflagellate symbioses was also used to measure host cell pHi and to determine the optimal pHi of isolated intact symbiosomes (i.e. the vacuoles that house the symbionts), as well as to compare the amounts of free glycerol and glucose (metabolites) present in the host tissues. Different host-symbiont combinations were found to have different photosynthetic and respiratory attributes. Earlier onset of full autotrophy (i.e. when all metabolic carbon demands of the symbiosis were met by photosynthesis) and higher CZAR values (i.e. the contribution of zooxanthellae to animal respiration) were demonstrated by symbioses hosting Symbiodinium B1 both from the original (homologous) and different (heterologous) host. The study showed that Symbiodinium types differ in their pH optima and that the optimal pHi for photosynthesis does not always match the actual measured pHi. Symbiont type was also shown to have an effect on host tissue glycerol and glucose pools, with the associations harbouring the homologous Symbiodinium B1 attaining the highest concentrations of both metabolites. Findings from this study suggest that corals may be able to maintain an association with a range of Symbiodinium types, and hence potentially switch as a consequence of bleaching. The new symbiont type may not be as nutritionally advantageous as the original type however, which could have implications for the growth and survivorship of the coral, unless it is able to supplement its carbon demands heterotrophically. The rapid proliferation of some of the heterologous Symbiodinium types (e.g. Symbiodinium E2) inside the host indicates that, after bleaching, there is potential for fast symbiont establishment. The reduced carbon contribution of these heterologous symbionts may not be a major concern should the coral be able to reinstate the more nutritionally advantageous symbiont as the dominant type during bleaching recovery. Finally, the rapid proliferation demonstrated by the heterologous Symbiodinium types and the associated metabolic cost to the host, could be an indication of the opportunistic nature of some of these types and may indicate a shift towards parasitism. It is imperative to extend this type of work to corals in the field to determine how these associations behave in nature. Also, in order to get a clearer picture of the diversity in symbiosis physiology, a wider range of Symbiodinium types needs to be investigated.</p>

Chlamydia pneumoniae-Induced Neuroinflammation Cell Model Using Lyophilized Cell-Free Supernatant v1

Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer's disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host's epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS.

The Basics of Infectious Diseases

Infectious Diseases result from exposure and contact between a host (human being) and an (uninvited) guest (micro-organism). Given the fact that billions of micro-organisms are in and around us at any time, overall, infectious diseases are comparatively rare; of the millions of different microbial species, only about 300 are known to cause human diseases. Besides exposure and contact, factors on the side of the host (genetic background, environment, underlying diseases and their therapy) and on the side of the micro-organisms (pathogenicity / virulence factors) are necessary to result in an infectious disease. “Colonization” means that a micro-organism can attach on skin or mucous membrane for some time or even indefinitely but does not invade host tissue and does not cause any symptoms. Colonizers may even induce an immune response. “Infection” is defined as a micro-organism invading through skin or mucous membranes the tissue of a host, leading to no disease (“asymptomatic infection”); or symptomatic disease. It is followed by health, disability, or death. Following the infection, microorganisms may persist in the body for a long time or even for life without causing any symptoms, which is called “latent infection”. Infectious diseases may not only be due to pathogenicity factors of a micro-organism, but may also result from (i.) direct destruction of host tissues (e.g., from viral replication); (ii.) the acute host (immune-) response; and from late immune responses resulting in immune-mediated “post-infectious diseases”. Some infections may cause an immune response that is directed against host-tissue, resulting in an “autoimmune-disease”. Given the increasing number of microbes, the increasing number of exposures, and the increasing number and fraction of susceptible/predisposed humans, it is obvious that infectious diseases will increase in the future. Vaccines and vaccination may help solve this problem.