Hispidulin Inhibits the Vascular Inflammation Triggered by Porphyromonas gingivalis Lipopolysaccharide.

Hispidulin is a natural bioactive flavonoid that has been studied for its potential therapeutic properties, including its anti-inflammatory, antioxidant, and neuroprotective effects. The aim of this study was to explore whether hispidulin could inhibit the endothelial inflammation triggered by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The adhesion of monocytes to the vascular endothelium was evaluated through in vitro and ex vivo monocyte adhesion assays. We analyzed the migration of monocytes across the endothelial layer using a transmigration assay. The results showed that treatment with hispidulin decreased the P. gingivalis LPS-induced adhesion of monocytes to endothelial cells and their migration by suppressing the P. gingivalis LPS-triggered expression of intercellular adhesion molecule-1 (ICAM-1) through downregulating nuclear factor-қB (NF-қB). In addition, hispidulin inhibited P. gingivalis LPS-induced mitogen-activated protein kinases (MAPKs) and AKT in endothelial cells. Altogether, the results indicate that hispidulin suppresses the vascular inflammation induced by P. gingivalis LPS. Mechanistically, it prevents the adhesion of monocytes to the vascular endothelium and migration and inhibits NF-қB, MAPKs, and AKT signaling in endothelial cells.

Analysis of Weather Factors on Aircraft Cancellation using a Multilayer Complex Network.

Airlines provide one of the most popular and important transportation services for passengers. While the importance of the airline industry is rising, flight cancellations are also increasing due to abnormal weather factors, such as rainfall and wind speed. Although previous studies on cancellations due to weather factors considered both aircraft and weather factors concurrently, the complex network studies only treated the aircraft factor with a single-layer network. Therefore, the aim of this study was to apply a multilayer complex network (MCN) method that incorporated three different factors, namely, aircraft, rainfall, and wind speed, to investigate aircraft cancellations at 14 airports in the Republic of Korea. The results showed that rainfall had a greater impact on aircraft cancellations compared with wind speed. To find out the most important node in the cancellation, we applied centrality analysis based on information entropy. According to the centrality analysis, Jeju Airport was identified as the most influential node since it has a high demand for aircraft. Also, we showed that characteristics and factors of aircraft cancellation should be appropriately defined by links in the MCN. Furthermore, we verified the applicability of the MCN method in the fields of aviation and meteorology. It is expected that the suggested methodology in this study can help to understand aircraft cancellation due to weather factors.

Experimental Investigation of Cavitation Bulk Nanobubbles Characteristics: Effects of pH and Surface-Active Agents.

Nanobubbles (NBs) have a widespread application in antimicrobial activity, wastewater treatment, and ecological restoration due to numerous peculiar characteristics, such as small diameter, long-term stability, and ability to produce hydroxyl radicals. Despite significant applications, only limited comprehensive investigations are available on the role of surfactants and pH in NBs characteristics. Therefore, this study examines the effects of different surfactants (i.e., anionic, cationic, and nonionic) and pH medium on bulk NB formation, diameter, concentration, bubble size distribution (BSD), ζ-potential, and stability. The effect of surfactant at concentrations above and below the critical micelle concentration was investigated. NBs were generated in deionized (DI) water using a piezoelectric transducer. The stability of NBs was assessed by tracking the variation in diameter and concentration over time. In a neutral medium, the diameter of NBs is smaller than in other surfactant or pH mediums. The diameter, concentration, BSD, and stability of NBs are strongly influenced by the ζ-potential rather than the solution medium. BSD curve shifts to a smaller bubble diameter when the magnitude of ζ-potential is high in any solution. In pure water, surfactant, and pH mediums, NBs have existed for a long time. NBs have a shorter life span in environments with a pH ≤ 3. Surfactant adsorption on the surface of NBs increases with increasing surfactant concentration up to a certain limit, beyond which it declines substantially. The Derjaguin-Landau-Verwey-Overbeek (DLVO) theory was used to interpret the NBs stability, resulting in a total potential energy barrier that is positive and greater than 45.55 kBT for 6 ≤ pH ≤ 11, whereas for pH < 6, the potential energy barrier essentially vanishes. Moreover, an effort has also been made to explicate the plausible prospect of ion distribution and its alignment surrounding NBs in cationic and anionic surfactants. This study will extend the in-depth investigation of NBs for industrial applications involving NBs.

A Review on Alternating Current Poling for Perovskite Relaxor-PbTiO3 Single Crystals.

With the great success on verifying its effectiveness on relaxor-PbTiO3 (PT) single crystals (SCs), alternating current poling (ACP) has been taking a center as a new domain engineering method in the last few years. Compared with the conventional direct current poling (DCP), ACP enables enhanced piezoelectric and dielectric properties. In this article, research progress in ACP and perspectives are introduced. Initially, optimized conditions of ACP for relaxor-PT SCs and unsolved issues on polycrystalline ceramics and spurious modes are reviewed. Second, the ferroelectric domain size dependence of piezoelectricity associated with ACP is discussed. We hypothesize that a tradeoff between domain and domain wall contributions exists for high piezoelectricity, suggesting an optimum 109° domain wall size, which is presumably dependent on compositions, crystallographic symmetries, and domain configurations. Finally, crystals synthesized by a solid-state crystal growth (SSCG) method are briefly introduced due to their unprecedented piezoelectricity obtained by ACP ( d33  âˆ¼ 5500 pC/N). We hope that this work helps to grasp the current status of ACP and to guide future tasks to be studied.

A Review of Lead Perovskite Piezoelectric Single Crystals and Their Medical Transducers Application.

Piezoelectric materials have been developed since early 1900s and many research had been conducted on the composition and process to obtain higher piezoelectric constants ( d33 ). Within composition research, lead perovskite relaxor piezoelectric single crystals (SCs) of Pb(Mg1/3Nb2/3)O3-lead titanate PbTiO3 type have been actively studied since 1990s because of their outstanding pC/N compared with those of the conventional Pb(Zr,Ti)O3 ceramics. A major driving force of these SC research has been promoted by mass production of ultrasound transducers and array probes for medical diagnostic systems since early 2000s. However, higher d33 material and process research for these ultrasound devices are almost saturated. In this review article, we present a brief overview of the history, current situation, and future perspective of piezoelectric SCs. The authors believe that the main research in the next century is high d33 SCs with a high composition uniformity and low-energy SC growth methods, such as solid-state SC growth, low-loss SC transducer manufacturing technique, and improved poling process. This is a big technical challenge for all the scientists; however, the relatively large market of medical ultrasound has been expanded year by year, and we hope that the community is motivated to solve such technical problems in the near future.

Chromosome-level de novo assembly of the pig-tailed macaque genome using linked-read sequencing and HiC proximity scaffolding.

BACKGROUND: Macaque species share >93% genome homology with humans and develop many disease phenotypes similar to those of humans, making them valuable animal models for the study of human diseases (e.g., HIV and neurodegenerative diseases). However, the quality of genome assembly and annotation for several macaque species lags behind the human genome effort. RESULTS: To close this gap and enhance functional genomics approaches, we used a combination of de novo linked-read assembly and scaffolding using proximity ligation assay (HiC) to assemble the pig-tailed macaque (Macaca nemestrina) genome. This combinatorial method yielded large scaffolds at chromosome level with a scaffold N50 of 127.5 Mb; the 23 largest scaffolds covered 90% of the entire genome. This assembly revealed large-scale rearrangements between pig-tailed macaque chromosomes 7, 12, and 13 and human chromosomes 2, 14, and 15. We subsequently annotated the genome using transcriptome and proteomics data from personalized induced pluripotent stem cells derived from the same animal. Reconstruction of the evolutionary tree using whole-genome annotation and orthologous comparisons among 3 macaque species, human, and mouse genomes revealed extensive homology between human and pig-tailed macaques with regards to both pluripotent stem cell genes and innate immune gene pathways. Our results confirm that rhesus and cynomolgus macaques exhibit a closer evolutionary distance to each other than either species exhibits to humans or pig-tailed macaques. CONCLUSIONS: These findings demonstrate that pig-tailed macaques can serve as an excellent animal model for the study of many human diseases particularly with regards to pluripotency and innate immune pathways.

Integrative Meta-Assembly Pipeline (IMAP): Chromosome-level genome assembler combining multiple de novo assemblies.

BACKGROUND: Genomic data have become major resources to understand complex mechanisms at fine-scale temporal and spatial resolution in functional and evolutionary genetic studies, including human diseases, such as cancers. Recently, a large number of whole genomes of evolving populations of yeast (Saccharomyces cerevisiae W303 strain) were sequenced in a time-dependent manner to identify temporal evolutionary patterns. For this type of study, a chromosome-level sequence assembly of the strain or population at time zero is required to compare with the genomes derived later. However, there is no fully automated computational approach in experimental evolution studies to establish the chromosome-level genome assembly using unique features of sequencing data. METHODS AND RESULTS: In this study, we developed a new software pipeline, the integrative meta-assembly pipeline (IMAP), to build chromosome-level genome sequence assemblies by generating and combining multiple initial assemblies using three de novo assemblers from short-read sequencing data. We significantly improved the continuity and accuracy of the genome assembly using a large collection of sequencing data and hybrid assembly approaches. We validated our pipeline by generating chromosome-level assemblies of yeast strains W303 and SK1, and compared our results with assemblies built using long-read sequencing and various assembly evaluation metrics. We also constructed chromosome-level sequence assemblies of S. cerevisiae strain Sigma1278b, and three commonly used fungal strains: Aspergillus nidulans A713, Neurospora crassa 73, and Thielavia terrestris CBS 492.74, for which long-read sequencing data are not yet available. Finally, we examined the effect of IMAP parameters, such as reference and resolution, on the quality of the final assembly of the yeast strains W303 and SK1. CONCLUSIONS: We developed a cost-effective pipeline to generate chromosome-level sequence assemblies using only short-read sequencing data. Our pipeline combines the strengths of reference-guided and meta-assembly approaches. Our pipeline is available online at http://github.com/jkimlab/IMAP including a Docker image, as well as a Perl script, to help users install the IMAP package, including several prerequisite programs. Users can use IMAP to easily build the chromosome-level assembly for the genome of their interest.

One-pot synthesis of silane-modified hyaluronic acid hydrogels for effective antibacterial drug delivery via sol-gel stabilization.

A silane-modified hyaluronic acid (HA) hydrogel was prepared using a facile one-pot method with 3-glycidyloxypropyl-trimethoxysilane (GPTMS). The sol-gel route, specifically the self-condensation of the silane, was combined with the HA hydrogel system to modify its network structure. Nuclear magnetic resonance (NMR) spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed the chemical functionalization of GPTMS. The morphological, rheological properties, and enzymatic degradation of the hydrogels were also evaluated. The sol-gel-stabilized HA hydrogel exhibited superior mechanical properties and biochemical stability as well as excellent biocompatibility without triggering any negative biological effects. Furthermore, an efficient drug-loading strategy is suggested that uses sol-gel encapsulation without the need for any chemical reagents, resulting in sustained release characteristics. Vancomycin was used as a model drug, and enhanced efficacy was demonstrated in antibacterial tests. The proposed approach is expected to have great potential for biomedical applications, and our findings will provide insight into the structure-property relationship of hydrogels.

Reflection-mode switchable subwavelength Bessel-beam and Gaussian-beam photoacoustic microscopy in vivo.

We have developed a reflection-mode switchable subwavelength Bessel-beam (BB) and Gaussian-beam (GB) photoacoustic microscopy (PAM) system. To achieve both reflection-mode and high resolution, we tightly attached a very small ultrasound transducer to an optical objective lens with numerical aperture of 1.0 and working distance of 2.5 mm. We used axicon and an achromatic doublet in our system to obtain the extended depth of field (DOF) of the BB. To compare the DOF performance achieved with our BB-PAM system against GB-PAM system, we designed our system so that the GB can be easily generated by simply removing the lenses. Using a 532 nm pulse laser, we achieved the lateral resolutions of 300 and 270 nm for BB-PAM and GB-PAM, respectively. The measured DOF of BB-PAM was approximately 229 µm, which was about 7× better than that of GB-PAM. We imaged the vasculature of a mouse ear using BB-PAM and GB-PAM and confirmed that the DOF of BB-PAM is much better than the DOF of GB-PAM. Thus, we believe that the high resolution achieved at the extended DOF by our system is very practical for wide range of biomedical research including red blood cell (RBC) migration in blood vessels at various depths and observation of cell migration or cell culture.

Precursor Phenomena of Barium Titanate Single Crystals Grown Using a Solid-State Single Crystal Growth Method Studied with Inelastic Brillouin Light Scattering and Birefringence Measurements.

The nature of precursor phenomena in the paraelectric phase of ferroelectrics is one of the main questions to be resolved from a fundamental point of view. Barium titanate (BaTiO3) is one of the most representative perovskite-structured ferroelectrics intensively studied until now. The pretransitional behavior of BaTiO3 single crystal grown using a solid-state crystal growth (SSCG) method was investigated for the first time and compared to previous results. There is no melting process in the SSCG method, thus the crystal grown using a SSCG method have inherent higher levels of impurity and defect concentrations, which is a good candidate for investigating the effect of crystal quality on the precursor phenomena. The acoustic, dielectric, and piezoelectric properties, as well as birefringence, of the SSCG-grown BaTiO3 were examined over a wide temperature range. Especially, the acoustic phonon behavior was investigated in terms of Brillouin spectroscopy, which is a complementary technique to Raman spectroscopy. The obtained precursor anomalies of the SSCG-grown BaTiO3 in the cubic phase were similar to those of other single crystals, in particular, of high-quality single crystal grown by top-seeded solution growth method. These results clearly indicate that the observed precursor phenomena are common and intrinsic effect irrespective of the crystal quality.

Facile strategy involving low-temperature chemical cross-linking to enhance the physical and biological properties of hyaluronic acid hydrogel.

Here, we present a novel strategy to fabricate hyaluronic acid (HA) hydrogels with excellent physical and biological properties. The cross-linking of HA hydrogel by butanediol diglycidyle ether (BDDE) was characterized under different reaction temperatures, and the resulting physical properties (i.e., the storage modulus and swelling ratio) were measured. The ratio between the cross-linking rate (a strengthening effect) and the hydrolysis rate (a weakening effect) was much greater with lower cross-linking temperatures after sufficient cross-linking time, resulting in a noticeably higher storage modulus. As the cross-linking temperature decreased, the formed HA hydrogel structure became denser with smaller pores. Moreover, the introduction of low-temperature HA cross-linking strategy also resulted in an enhanced several important characteristics of HA hydrogels including its enzymatic resistivity and its ability to elicit a cellular response. These results indicate the performance of HA hydrogels can be markedly enhanced without further additives or modifications, which is expected to contribute to the advancement of applications of HA hydrogels in all industrial fields.

Enhancement of bio-stability and mechanical properties of hyaluronic acid hydrogels by tannic acid treatment.

Hyaluronic acid (HA) has been widely investigated because of its excellent biocompatibility and its ability to form hydrogels with various chemical modifications. However, HA hydrogels undergo rapid degradation and exhibit poor mechanical stability under physiological conditions. Tannic acid (TA), a naturally occurring polyphenol found in plants and fruits, has recently attracted interest as a crosslinking agent because of its abundant hydroxyl groups. In this study, we prepared HA hydrogels chemically crosslinked by polyethylene glycol diglycidyl ether (PEGDE) and treated with TA in an attempt to enhance the physical properties of HA hydrogels. TA acts as a physical crosslinker owing to the strong hydrogen bonding between TA and PEGDE, resulting in improved mechanical properties that support both cell attachment and proliferation without any sign of cytotoxicity. The enzymatic stability of the HA-TA hydrogels was significantly enhanced with the addition of TA, which was attributed to the hyaluronidase inhibition activity of TA. Additionally, the antioxidant potential of TA resulted in good resistance to degradation by reactive oxygen species, which can be generated in human tissues.

Self-Growth of Centimeter-Scale Single Crystals by Normal Sintering Process in Modified Potassium Sodium Niobate Ceramics.

In this manuscript, an interesting phenomenon is reported. That is the self-growth of single crystals in Pb-free piezoelectric ceramics. These crystals are several centimeters in size. They are grown without any seed addition through a normal sintering process in modified potassium sodium niobate ceramics. It has been achieved by the composition designed to compensate the Na(+) loss which occurs during the liquid phase sintering. The composition of the crystals is (K0.4925Na(0.4925-x)Ba(0.015+x/2))Nb(0.995+x)O3 [x is determined by the Na(+) loss, due to Na2O volatilization]. These crystals have high piezoelectric voltage coefficients (g33, 131 10(-3)Vm/N), indicating that they are good candidates for piezoelectric sensors and energy harvesting devices. We hope that this report can offer the opportunity for many researchers to have an interest in these crystals.

Lactobacillus plantarum HY7712 protects against the impairment of NK-cell activity caused by whole-body γ-irradiation in mice.

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-kappaB-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body γ-irradiated mice. Exposure to HY7712 strongly activated NF-kappaB signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-kappaB activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-γ and upregulation of interleukin (IL)-13 caused by γ-irradiation in mice. In mice, γ-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-kappaB signaling pathway and protects against the impairment of NK-cell activity caused by γ-irradiation or aging.

Targeted ablation of the histidine-rich Ca(2+)-binding protein (HRC) gene is associated with abnormal SR Ca(2+)-cycling and severe pathology under pressure-overload stress.

The histidine-rich Ca(2+)-binding protein (HRC) is located in the lumen of the sarcoplasmic reticulum (SR) and exhibits high-capacity Ca(2+)-binding properties. Overexpression of HRC in the heart resulted in impaired SR Ca(2+) uptake and depressed relaxation through its interaction with SERCA2a. However, the functional significance of HRC in overall regulation of calcium cycling and contractility is not currently well defined. To further elucidate the role of HRC in vivo under physiological and pathophysiological conditions, we generated and characterized HRC-knockout (KO) mice. The KO mice were morphologically and histologically normal compared to wild-type (WT) mice. At the cellular level, ablation of HRC resulted in significantly enhanced contractility, Ca(2+) transients, and maximal SR Ca(2+) uptake rates in the heart. However, after-contractions were developed in 50 % of HRC-KO cardiomyocytes, compared to 11 % in WT mice under stress conditions of high-frequency stimulation (5 Hz) and isoproterenol application. A parallel examination of the electrical activity revealed significant increases in the occurrence of Ca(2+) spontaneous SR Ca(2+) release and delayed afterdepolarizations with ISO in HRC-KO, compared to WT cells. The frequency of Ca(2+) sparks was also significantly higher in HRC-KO cells with ISO, consistent with the elevated SR Ca(2+) load in the KO cells. Furthermore, HRC-KO cardiomyocytes showed significantly deteriorated cell contractility and Ca(2+)-cycling caused possibly by depressed SERCA2a expression after transverse-aortic constriction (TAC). Also HRC-null mice exhibited severe cardiac hypertrophy, fibrosis, pulmonary edema and decreased survival after TAC. Our results indicate that ablation of HRC is associated with poorly regulated SR Ca(2+)-cycling, and severe pathology under pressure-overload stress, suggesting an essential role of HRC in maintaining the integrity of cardiac function.

Lactobacillus plantarum HY7712 ameliorates cyclophosphamide-induced immunosuppression in mice.

Lactic acid bacteria (LAB) in fermented foods have attracted considerable attention recently as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of 500 strains of LAB, isolated from kimchi, to induce TNF--α production in peritoneal macrophages was investigated. Lactobacillus plantarum HY7712 most strongly induced TNF--α production as well as NF-κB activation. However, HY7712 inhibited NF-κB activation in LPS-stimulated peritoneal macrophages. When HY7712 was orally treated in cyclophosphamide (CP)-immunosuppressed mice for 5 or 15 days, it reversed the body and spleen weights, blood RBC and WBC levels, and splenocyte and bone marrow cells that were reduced by CP. Orally administered HY7712 increased concanavalin A-induced T cell proliferation to 84.5% of the normal group on day 15, although treatment with CP alone markedly reduced it to 53.7% of the normal group. Furthermore, orally administered HY7712 significantly induced the expressions of IL-2 and IFN-γ in ConA-induced splenic cytotoxic T cells of CP-treated mice. Orally administered HY7712 restored the CP-impaired phagocytosis of macrophages in mice. Orally administered HY7712 also restored the cytotoxicity of NK and cytotoxic T cells derived from spleen and bone marrow against YAC-1 in CP-immunosuppressed mice. Based on these findings, orally administered HY7712 may accelerate the recovery of cyclophosphamide-caused immunosuppression, without evident side effects, by immunopotentiating NK and Tc cells, and may provide a mechanistic basis for using HY7712 as an alternative means in lessening chemotherapyinduced immunosuppression in cancer patients.

1H NMR-based metabonomic assessment of probiotic effects in a colitis mouse model.

Metabolic profiling of the fecal extracts of male mice was carried out to assess the effects of probiotics on colonic inflammation using (1)H NMR spectroscopy coupled with multivariate data analysis. The control group (n = 5) was administered phosphate buffered saline for 14 days. Acute colitis was induced with dextran sulfate sodium (DSS) for 7 days following administration of phosphate buffered saline for 7 days (DSS-treated group, n = 5). LAB + DSS-treated group (n = 5) was administered lactic acid bacteria (LAB) daily for 7 days followed by treatment with DSS for 7 days to investigate protective effect of LAB against DSS-inducible colitis. Histological damage, myeloperoxidase activity, and malondialdehyde content of colon tissue were reduced, whereas colon length increased in LAB + DSS-treated mice compared to those in DSS-treated mice. DSS treatment was associated with fecal excretion of amino acids, short chain fatty acids, and nucleotides, revealing significant decreases of threonine, alanine, glutamate, glutamine, aspartate, lysine, glycine, butyrate, uracil, and hypoxanthine together with increases of monosaccharides, glucose, and trimethylamine in the feces of mice with DSS-induced colitis. Increased levels of acetate, butyrate, and glutamine and decreased levels of trimethylamine were found in the feces of LAB + DSS-treated mice compared to DSS-treated mice alone. The increased short chain fatty acids levels in the feces of mice fed with LAB indicate that the probiotics have protective effects against DSS-induced colitis via modulation of the gut microbiota. This work highlights the possibility for alternative approach of metabonomics in feces for assessing the probiotic effect in an animal model of inflammatory bowel disease.

Bifidobacterium longum HY8004 attenuates TNBS-induced colitis by inhibiting lipid peroxidation in mice.

OBJECTIVE: To investigate the mechanisms of the preventive activity of lactic acid bacteria in colitis, the inhibitory effect of Bifidobacterium longum HY8004, which potently inhibited lipid peroxidation in vitro, was examined in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. METHODS: We measured the ability of lactic acid bacteria (LAB) to inhibit lipid peroxidation in vitro and to inhibit colitis outcomes, colon shortening, and myeloperoxidase activity in TNBS-induced colitis in C3H/HeN and C3H/HeJ mice. We also measured levels of the inflammatory markers interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha and their transcription factor, NF-kappaB, in the colon by enzyme-linked immunosorbent assay and immunoblot analysis. RESULTS: Among the LAB tested, B. logum HY8004 most potently inhibited lipid peroxidation in vitro but did not inhibit TLR-4-linked NF-kappaB activation in HEK cells. Oral administration of HY8004 inhibited TNBS-induced colon shortening and myeloperoxidase activity in the colon of C3H/HeN and C3H/HeJ mice as well as IL-1 beta and TNF-alpha expression. B. longum HY8004 also inhibited TNBS-induced lipid peroxidation, TLR-4 expression, and NF-kappaB activation in the colon of C3H/HeN and C3H/HeJ mice. CONCLUSION: B. longum HY8004 can improve colitis via the inhibition of lipid peroxidation as well as NF-kappaB activation.

Evaluation of anti-colitic effect of lactic acid bacteria in mice by cDNA microarray analysis.

To evaluate the anti-colitic effect of lactic acid bacteria by cDNA microarray analysis, a lactic acid bacteria mixture (LM) consisting of Lactobacillus brevis HY7401, L. suntoryeus HY7801 and Bifidobacterium longum HY8004 was orally administered to dextran sulfate (DSS)-induced colitic mice and the expression profile of numerous genes was assessed. DSS treatment caused colitic outcomes such as inflammation and colon shortening. DSS also up-regulated the expression of inflammation-related genes: pro-inflammatory and chemotactic cytokines, including IL-1beta, TNF-alpha, IL-6, CCL2, CCL4, CCL7, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and their receptors CCR3 and CCR7, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1. LM treatment inhibited the mRNA expression of inflammation-related and tissue remodeling genes induced by DSS as well as the colitic symptoms. LM inhibition for the DSS-induced expression of the representative inflammatory markers, IL-1beta, TNF-alpha and COX-2, was supported by quantitative real-time polymerase chain reaction analysis. These findings suggest that LM ameliorates DSS-induced colitis by regulating inflammatory-related cytokines as well as tissue remodeling genes.

Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-kappaB activation in experimental colitis.

OBJECTIVE: Lactic acid bacteria (LAB) can improve disturbances of indigenous microflora as well as inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. We examined the anticolitic effect of Lactobacillus suntoryeus HY7801, which inhibited toll-like receptor (TLR)-4-linked NF-kappaB activation in human embryonic kidney (HEK) cells, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitic mice. MATERIALS AND METHODS: We measured the ability of commercial and intestinal LAB to inhibit lipopolysaccharide (LPS)-stimulated, TLR-4-linked NF-kappaB activation in HEK cells, as well as to inhibit colitis outcomes in TNBS-induced colitic mice. We also measured levels of the inflammatory markers, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6, and their transcription factor, NF-kappaB, in intestinal mucosa by enzyme-linked immunosorbent assay and immunoblotting. RESULTS AND DISCUSSION: LAB inhibited TLR-4-linked NF-kappaB activation, and L. suntoryeus HY7801 was the most potent inhibitor. Intrarectal treatment of TNBS in mice caused colon shortening and also increased colonic expression of IL-1beta, IL-6, and TNF-alpha expression. However, oral administration of Lactobacillus HY7801 (100 mg/kg) inhibited colon shortening (p < 0.001) and myeloperoxidase activity in TNBS-induced colitic mice (p < 0.0002) and also decreased colonic expression of IL - 1beta (p < 0.003), IL-6 (p < 0.0001), and TNF-alpha (p < 0.0001). Lactobacillus HY7801 inhibited the NF-kappaB activation and TLR-4 expression induced by TNBS, as well as the expression of cyclooxygenase 2. Lactobacillus HY7801 also reduced the activity of intestinal bacterial glycosaminoglycan degradation and beta-glucuronidase induced by TNBS. CONCLUSION: L. suntoryeus HY7801 can improve colitis via the inhibition of TLR-4-linked NF-kappaB activation.