Tissues within the central nervous system (CNS) have generally been regarded as immunologically privileged. However, in recent decades, it has been shown that immune reactions in the CNS continuously ...occur via various types of inflammation following autoimmune diseases and mechanical insults such as spinal cord injury (SCI). Among the various inflammatory cells associated with CNS disease, activated macrophages are classically known to induce detrimental consequences that are mediated by the secretion of pro-inflammatory molecules. Alternatively activated macrophages have recently been shown to modulate various types of CNS inflammation, including SCI. This review summarizes the potential roles of alternatively activated macrophages in the course of CNS inflammation in rodent SCI models.
In the current study, a hemispherical shell vapor chamber (HSVC) was proposed and manufactured. A unique system of the HSVC consists of a very short evaporator space and a large condenser area with ...an inner and outer surface. The HSVC has a bottom surface that can be easily attached to the heat source and its radius varies from 0.045 m (near the bottom surface) to 0.078 m at the top with a curved side. An entirely new design of the integrated section of the large condenser with the evaporator section was verified using a new but simple concept. The current hemispherical shell vapor chamber (HSVC) was made from stainless steel. The current HSVC was specified with an outer/inner diameter of 78/70 mm at the top, a depth of 47 mm in the inner surface area, a total height of 60 mm, 30 mm at the bottom of the inner center, and a diameter of 45 mm on the surface of the outer bottom area. Three different models were manufactured and tested to verify which HSVC reached a high thermal performance. The effects of various operation parameters such as the filled volume ratio, heat load, coolant flow velocity, orientation, and so forth, were investigated experimentally. The experimental results showed that the optimum charge amount in terms of temperature difference is 20–30% of the charging ratio, and the condenser area has a direct effect on the thermal performance. Moreover, a one-dimensional thermal resistance model was tested to predict and simulate the thermal performance of the current system associated with various empirical correlations. Furthermore, the CFD (Computational Fluid Dynamics) model can simulate a lot of detailed flow behavior inside the HSVC. Both simulation methods can predict the thermal performance of the HSVC, and they can help to design the system with a focus on the optimum configuration of the design target for any application.
Enterococcus faecalis
, a Gram-positive bacterium commonly isolated in patients with refractory apical periodontitis, invades dentin tubules easily and forms biofilms. Bacteria in biofilms, which ...contribute to recurrent and/or chronic inflammatory diseases, are more resistant to antimicrobial agents than planktonic cells and easily avoid phagocytosis. Although
Lactobacillus plantarum
lipoteichoic acid (Lp.LTA) is associated with biofilm formation, the effect of Lp.LTA on biofilm formation by
E. faecalis
is not clearly understood. In this study, we investigated whether Lp.LTA inhibits
E. faecalis
biofilm formation. The degree of biofilm formation was determined by using crystal violet assay and LIVE/DEAD bacteria staining. The quantification of bacterial growth was determined by measuring the optical density at 600 nm with a spectrophotometer. Formation of biofilms on human dentin slices was observed under a scanning electron microscope.
E. faecalis
biofilm formation was reduced by Lp.LTA treatment in a dose-dependent manner. Lp.LTA inhibited biofilm development of
E. faecalis
at the early stage without affecting bacterial growth. LTA from other
Lactobacillus
species such as
Lactobacillus acidophilus, Lactobacillus casei
, or
Lactobacillus rhamnosus
GG also inhibited
E. faecalis
biofilm formation. In particular, among LTAs from various lactobacilli, Lp.LTA showed the highest inhibitory effect on biofilms formed by
E. faecalis
. Interestingly, LTAs from lactobacilli could remove the biofilm preformed by
E. faecalis
. These inhibitory effects were also observed on the surface of human dentin slices. In conclusion, Lactobacillus species LTA inhibits biofilm formation caused by
E. faecalis
and it could be used as an anti-biofilm agent for prevention or treatment against
E. faecalis
-associated diseases.
Abstract Introduction Streptococcus gordonii is a predominant member of the oral microflora and has been isolated from root canals of teeth with refractory apical periodontitis. Biofilm formation is ...important for various dental diseases, and S. gordonii is involved in dental biofilm formation as an early colonizer. Although serine-rich repeat (SRR) adhesins of S. gordonii such as gordonii surface protein B (GspB) are associated with bacterial colonization, the role of GspB in biofilm formation is not clearly understood. In the present study, we investigated the effect of S. gordonii GspB on biofilm formation using wild-type and GspB-deficient mutant S. gordonii strains. Methods Confocal microscopy and crystal violet assay were used to determine biofilm formation. Bacterial growth was examined by measuring optical density with spectrometry. Bacterial adherence and biofilm on the culture plate and human dentin slices were visualized with a scanning electron microscope. Results The GspB-deficient S. gordonii mutant strain was less potent than the wild-type strain in biofilm formation. Of note, there was no difference in the bacterial growth rate between the mutant and wild-type strains. Differences in biofilm-forming ability between the wild-type and mutant strains were more distinct in the sucrose-supplemented media. Furthermore, the GspB-deficient mutant exhibited attenuated formation of aggregates on the surface of the culture plate and human dentin slices. Conclusions These results suggest that GspB is important for S. gordonii biofilm formation, which may contribute to the development of dental biofilm-associated diseases.
Salmonella enterica
is a leading cause of food-borne diseases in humans worldwide, resulting in severe morbidity and mortality. They are carried asymptomatically in the intestine or gallbladder of ...livestock, and are transmitted predominantly from animals to humans
via
the fecal-oral route. Thus, the best preventive strategy is to preemptively prevent transmission to humans by vaccinating livestock. Live attenuated vaccines have been mostly favored because they elicit both cellular and humoral immunity and provide long-term protective immunity. However, developing these vaccines is a laborious and time-consuming process. Therefore, most live attenuated vaccines have been mainly used for phenotypic screening using the auxotrophic replica plate method, and new types of vaccines have not been sufficiently explored. In this study, we used Radiation-Mutation Enhancement Technology (R-MET) to introduce a wide variety of mutations and attenuate the virulence of
Salmonella
spp. to develop live vaccine strains. The
Salmonella
Typhimurium, ST454 strain (ST WT) was irradiated with Cobalt
60
gamma-irradiator at 1.5 kGy for 1 h to maximize the mutation rate, and attenuated daughter colonies were screened using
in vitro
macrophage replication capacity and
in vivo
mouse infection assays. Among 30 candidates, ATOMSal-L6, with 9,961-fold lower virulence than the parent strain (ST454) in the mouse LD
50
model, was chosen. This vaccine candidate was mutated at 71 sites, and in particular, lost one bacteriophage. As a vaccine, ATOMSal-L6 induced a
Salmonella
-specific IgG response to provide effective protective immunity upon intramuscular vaccination of mice. Furthermore, when mice and sows were orally immunized with ATOMSal-L6, we found a strong protective immune response, including multifunctional cellular immunity. These results indicate that ATOMSal-L6 is the first live vaccine candidate to be developed using R-MET, to the best of our knowledge. R-MET can be used as a fast and effective live vaccine development technology that can be used to develop vaccine strains against emerging or serotype-shifting pathogens.
Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid arthritis patients annually in ...Europe. Several recent clinical trials have reported that LDRT can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. However, the therapeutic mechanism of LDRT remains unelucidated. Therefore, in the current study, we aimed to investigate the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT. Mice were irradiated to the whole lung 1 day post-infection. The changes in levels of inflammatory mediators (cytokines and chemokines) and immune cell populations in the bronchoalveolar lavage (BALF), lungs, and serum were examined. LDRT-treated mice displayed markedly increased survival rates and reduced lung edema and airway and vascular inflammation in the lung; however, the viral titers in the lungs were unaffected. Levels of primary inflammatory cytokines were reduced after LDRT, and transforming growth factor-β (TGF-β) levels increased significantly on day 1 following LDRT. Levels of chemokines increased from day 3 following LDRT. Additionally, M2 macrophage polarization or recruitment was increased following LDRT. We found that LDRT-induced TGF-β reduced the levels of cytokines and polarized M2 cells and blocked immune cell infiltration, including neutrophils, in BALF. LDRT-induced early TGF-β production was shown to be a key regulator involved in broad-spectrum anti-inflammatory activity in virus-infected lungs. Therefore, LDRT or TGF-β may be an alternative therapy for viral pneumonia.
•S. gordonii LTA or lipoproteins unaffected bacterial morphology, size, or growth.•Δlgt weakly induced proinflammatory cytokines in macrophages.•S. gordonii lipoproteins potently induced ...proinflammatory cytokines via TLR2.•Δlgt was less virulent than the wild-type S. gordonii or ΔltaS in vivo.
Gram-positive bacteria such as Streptococcus gordonii causing life-threatening infective endocarditis are mainly recognized by Toll-like receptor 2 (TLR2). Lipoteichoic acid (LTA) and lipoproteins are representative TLR2 ligands that play important roles in bacterial infection and in host inflammatory responses. In the present study, we generated an LTA-deficient mutant (ΔltaS) and a lipoprotein-deficient mutant (Δlgt) and investigated the contributions of LTA and lipoproteins to bacterial morphology and their effect on induction of proinflammatory cytokines in THP-1 and mouse bone-marrow derived macrophages (BMDMs). Deletion of ltaS and lgt was confirmed by PCR analysis of genomic DNA from each mutant. The mutants with absence of LTA or lipoproteins were examined by SDS-PAGE followed by Western blotting with anti-LTA antibodies and silver staining, respectively. Interestingly, scanning and transmission electron microscopies showed no difference in the bacterial cell morphology or size between the wild-type and the mutants even though substantial changes in the cell size and/or morphology have been reported in other Gram-positive bacteria such as Staphylococcus aureus, Listeria monocytogenes, and Bacillus subtilis. However, S. gordonii wild-type and ΔltaS potently induced the expression of proinflammatory cytokines including TNF-α, IL-8, and IL-1β at the mRNA and protein levels, while Δlgt did not have these effects. Furthermore, lipoproteins purified from S. gordonii also induced the expression of the aforementioned cytokines more potently than the purified LTA. Neither LTA nor lipoprotein induced TNF-α, KC (IL-8 counterpart in mouse), and IL-1β in TLR2-deficient BMDMs. S. gordonii Δlgt was less virulent than the wild-type or ΔltaS in a mouse intraperitoneal infection model. Collectively, these results suggest that S. gordonii lipoproteins, but not LTA, are mainly responsible for the infection and inflammatory responses.
We previously demonstrated that the receptor for the complement component C1q (gC1qR) is a lipid raft protein that is indispensable for adipogenesis and insulin signaling. Here, we provide the first ...report that gC1qR is an essential component of lamellipodia in human lung carcinoma A549 cells. Cell-surface gC1qR was concentrated in the lamellipodia along with CD44, monosialoganglioside, actin, and phosphorylated focal adhesion kinase in cells stimulated with insulin, IGF-1, EGF, or serum. The growth factor-induced lamellipodia formation and cell migration were significantly decreased in gC1qR-depleted cells, with a concomitant blunt activation of the focal adhesion kinase and the respective receptor tyrosine kinases. Moreover, the gC1qR-depleted cells exhibited a reduced proliferation rate in culture as well as diminished tumorigenic and metastatic activities in grafted mice. We therefore conclude that cell-surface gC1qR regulates lamellipodia formation and metastasis via receptor tyrosine kinase activation.
There is a substantial need for the development of biomaterials for protecting hematopoietic stem cells and enhancing hematopoiesis after radiation damage. Bacterial exopolysaccharide (EPS) has been ...shown to be very attractive to researchers as a radioprotectant owing to its high antioxidant, anti-cancer, and limited adverse effects. In the present study, we isolated EPS from a novel strain,
Deinococcus radiodurans
BRD125, which produces EPS in high abundance, and investigated its applicability as a radioprotective biomaterial. We found that EPS isolated from EPS-rich
D. radiodurans
BRD125 (DeinoPol-BRD125) had an excellent free-radical scavenging effect and reduced irradiation-induced apoptosis. In addition, bone-marrow and spleen-cell apoptosis in irradiated mice were significantly reduced by DeinoPol-BRD125 administration. DeinoPol-BRD125 enhanced the expression of hematopoiesis-related cytokines such as GM-CSF, G-GSF, M-CSF, and SCF, thereby enhancing hematopoietic stem cells protection and regeneration. Taken together, our findings are the first to report the immunological mechanism of a novel radioprotectant, DeinoPol-BRD125, which might constitute an ideal radioprotective and radiation mitigating agent as a supplement drug during radiotherapy.
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