1,721,015 research outputs found
Interleukin-10 and its receptors at the maternal-conceptus interface: expression, regulation, and implication for T helper 2 cytokine predominance and maternal immune tolerance in the pig, a true epitheliochorial placentation species
No full text© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: [email protected] appropriate balance between pro-inflammatory and anti-inflammatory cytokines is important for the maternal immune tolerance during pregnancy in mammals. Among the various cytokines, interleukin (IL)-10 (IL10) plays an essential role in anti-inflammatory responses, while IL12 is involved in pro-inflammatory responses during pregnancy. However, the roles of IL10 and IL12 in the endometrium during pregnancy have not been studied in pigs. Thus, we investigated the expression of IL10, IL12 (IL12A and IL12B), and their receptors (IL10RA, IL10RB, IL12RB1, and IL12RB2) at the maternal-conceptus interface. IL10, IL12, and their receptors were expressed in the endometrium during the estrous cycle and pregnancy in a pregnancy stage-specific manner. During pregnancy, IL10 expression increased on Day 15, whereas the expression of IL12A and IL12B decreased after the implantation period. IL10 protein was localized to luminal epithelial (LE), stromal cells, and macrophages; IL10RA protein to LE, endothelial, stromal, and T cells; and IL10RB mRNA to LE cells in the endometrium. IL10 and IL10RA proteins and IL10RB mRNA were also localized to chorionic epithelial (CE) cells. In endometrial explants, the expression of IL10RA and IL10RB was induced by estradiol-17β, IL-1β, and/or interferon-γ. Heme oxygenase 1, an IL10-inducible factor, was expressed in the endometrium with the highest levels on Day 30 of pregnancy and was localized to LE and CE cells. These results in pigs suggest that conceptus-derived signals change the endometrial immune environment by regulating the expression of IL10 and IL10 receptors at the maternal-conceptus interface and that IL10 may provide anti-inflammatory conditions for the maternal immune tolerance.N
Poly(beta-amino ester) as a carrier for si/shRNA delivery in lung cancer cells
No full textEfficient delivery of small interfering RNA (siRNA) or small hairpin RNA (shRNA) is a critical concern in RNA interference (RNAi) studies. In the present study, we evaluated biodegradable poly(beta-amino ester) (PAE) carrier composed of low molecular weight polyethylenimine and poly(ethylene glycol) for si/shRNA delivery in lung cancer cells. PAE carrier successfully delivered EGFP (enhanced green fluorescence protein) siRNA (siGFP) and silenced EGFP expression. The silencing achieved with PAE carrier was found to be nearly 1.5 times superior and safer than standard PEI25K. Also, our PAE carrier exhibited superior Akt1 shRNA delivery (shAkt) and thereby silenced oncoprotein Akt1 efficiently. PAE-shAkt mediated Akt1 knock-down hindered cancer cell growth in Akt1 specific manner. Superior shAkt delivery and low cytotoxicity of PAE carrier promoted Akt1 knock-down specific apoptosis, while low delivery efficiency and high cytotoxicity of PEI25K carrier mainly exhibited undesirable necrosis. Moreover, basic cancer properties like cell proliferation, malignancy and metastasis were reduced more efficiently using PAE-shAkt system. These findings demonstrated the potential of PAE as an alternative to PEI25K in si/shRNA-based RNAi studies. (c) 2008 Elsevier Ltd. All rights reserved.N
Mutagenicity and immune toxicity of emulsion-type sausage cured with plasma-treated water
No full textCold plasma has been developed to reduce microbial contamination and to improve safety of food and medical products. In addition, the technology can be used in the manufacture of sausages without addition of nitrite. To be applied in food industry commercially, the new technology should be safe and efficient. However, toxicological test of plasma-treated food is limited. Therefore, the purpose of this study was to determine the mutagenicity and immune toxicity of the meat products cured with plasma-treated water (PTW) as a nitrite source. Emulsion sausages were prepared with no nitrite (control), sodium nitrite (SCS), and PTW (SCP). For a mutagenicity test, the Ames test was performed with the sausage samples. For immune toxicity test, 8-wk-old female Balb/c mice were given free access to the sausages in order to evaluate the tumor necrosis factor (TNF)-alpha level. As a result, no mutagenicity was detected in the sausages by the Ames test. The serum TNF-alpha values were less than 10 pg/mL in mice after feeding control and treated samples for 32 d, indicating that no inflammatory response was occurred by feeding the sausages made by PTW. Therefore, the present study opens the possibility of using plasma-treated water as a nitrite source without any toxicity.Y
The effect of RNAi silencing of p62 using an osmotic polysorbitol transporter on autophagy and tumorigenesis in lungs of K-ras(LA1) mice
No full textTreating cancer patients by conventional chemotherapy to achieve prolonged survival still remains complicated. Autophagy is a topic of considerable interest in recent times, as it may contribute greatly to tumor suppression. Recent studies indicate that autophagy-deficient cells accumulate high levels of p62, an ubiquitin-binding scaffold protein, involved greatly in tumorigenesis. Here, we synthesized an osmotically active polysorbitol-mediated transporter (PSMT) to downregulate p62 using an RNAi strategy and described the mechanism of how p62 silencing using PSMT/siRNA p62 system activates autophagy and contributes to tumor suppression in the lungs of K-ras(LA1) mice. Downregulation of p62 by PSMT/siRNA p62 activated autophagy confirmed by the formation of autophagosomes and swelling of Golgi apparatus with a decreasing level of GM130, a cis-Golgi matrix protein. Activation of osmotic PSMT-mediated autophagy remarkably reduced the size and number of tumors by suppressing proliferative cell nuclear antigen, cluster of differentiation 31, and vascular endothelial growth factor levels. Furthermore, an increase in apoptosis was observed in the lungs of PSMT/siRNA p62-delivered mice. (C) 2013 Elsevier Ltd. All rights reserved.N
Heat-killed Lancefieldella Rimae Induces Bone Resorption by Promoting Osteoclast Differentiation
No full textIntroduction: Apical periodontitis, mainly caused by bacterial infection in the dental pulp, is often accompanied by abscess, periapical inflammation, and alveolar bone loss. Lancefieldella rimae has been detected in the root canals of patients with apical periodontitis. Here, we investigated whether L. rimae is associated with bone resorption. Methods: L. rimae was anaerobically cultured and heat-killed (HKLr). A mouse calvarial implantation model was used to determine the bone resorption in vivo. Committed osteoclasts prepared from C57BL/6 wild-type or Toll-like receptor 2 (TLR2)-deficient mice were differentiated into mature osteoclasts in the presence or absence of HKLr. The mRNA expression of tartrate-resistant acid phosphatase (TRAP), ATPase H+ transporting V0 subunit D2, cathepsin K, interleukin-6, tumor necrosis factor-a, and glyceraldehyde 3-phosphate dehydrogenase was quantified using real-time reverse transcription-polymerase chain reaction. The protein levels of c-Fos and NFATc1 were determined by Western blot analysis. Results: Implantation of HKLr onto the mouse calvaria induced the bone destruction with an increase of TRAP-positive areas. While HKLr enhanced the differentiation of osteoclasts, this effect was not observed in TLR2deficient osteoclasts. HKLr dose-dependently increased the mRNA expression of genes associated with osteoclast differentiation including TRAP, ATPase H+ transporting V0 subunit D2, and cathepsin K. In addition, HKLr enhanced the expression of c-Fos and NFATc1, which are important transcription factors for osteoclast differentiation. Moreover, HKLr increased the expression of interleukin-6 and tumor necrosis factor-a. Conclusion: L. rimae induces bone resorption by enhancing osteoclast differentiation through the TLR2 signaling pathway, implying that L. rimae is a causative agent responsible for the alveolar bone resorption accompanying apical periodontitis. (J Endod 2024;50:1593-1601.)N
Lactobacillus plantarum lipoteichoic acid disrupts mature Enterococcus faecalis biofilm
No full textApical periodontitis is caused by biofilm-mediated root canal infection. Early phase oral bacterial biofilms are inhibited by Lactobacillus plantarum lipoteichoic acid (Lp.LTA). However, mature biofilms that develop over 3 weeks are more resistant to traditional endodontic medicaments. Therefore, this study examined the effectiveness of Lp.LTA on disrupting mature Enterococcus faecalis biofilms, and on enhancing the effects of endodontic medicaments. LTA was purified from L. plantarum through butanol extraction followed by hydrophobic and ion-exchange chromatography. E. faecalis biofilms were formed over 3 weeks on glass bottom dishes and in dentin blocks obtained from human single-rooted premolars. These mature biofilms were treated with or without Lp.LTA for 1 h, followed by additional treatment with either chlorhexidine digluconate (CHX), calcium hydroxide (CH), or triple antibiotics for 24 h. Biofilms on glass were live/dead stained and quantified by ZEN through confocal laser microscopy. Bio-films in dentin were fixed, sputter coated and analyzed by ImageJ with scanning electron microscopy. Preformed E. faecalis mature biofilms on the culture dishes were dose-dependently disrupted by Lp.LTA. Lp.LTA potentiated the effects of CHX or CH on the disruption of mature biofilm. Interestingly, CHX-induced disruption of preformed E. faecalis mature biofilms was synergistically enhanced only when pre-treated with Lp.LTA. Furthermore, in the dentin block model, Lp.LTA alone reduced E. faecalis mature biofilm and pre-treatment with Lp.LTA promoted the anti-biofilm activity of CHX. Lp.LTA could be an anti-biofilm or supplementary agent that can be effective for E. faecalis-biofilm-induced diseases.N
Essential cues of engineered polymeric materials regulating gene transfer pathways
No full textRegulating cellular uptake pathways using engineered materials is becoming a vital strategy for efficient gene transfer because the success of gene delivery most often relies on the uptake mechanism and the intracellular fate of the delivery vectors. The uptake of gene carriers can be greatly affected by the various physical, geometrical, chemical, and biological characteristics of the delivery vectors. In the design of gene delivery materials, especially polymeric materials, it is important to understand not only how gene carriers are taken up and transported into cells, but also how the uptake mechanism can be regulated. In this review, we discuss polymeric materials that regulate cellular uptake pathways for highly effective delivery of gene therapeutics, elucidate various routes of cellular uptake that alter the intracellular fate of polymeric gene carriers and finding efficient strategies for overcoming extracellular and intracellular obstacles. We also discuss the structures of polymeric materials in order to understand how they regulate cellular uptake. Lastly, we discuss various strategic approaches, including essential cues on how to regulate the cellular uptake pathways of polymeric carriers and how to control their endocytic trafficking to improve the efficacy of gene delivery
The role of osmotic polysorbitol-based transporter in RNAi silencing via caveolae-mediated endocytosis and COX-2 expression
No full textPolymeric diversity allows us to design gene carriers as an alternative to viral vectors, control cellular uptake, target intracellular molecules, and improve transfection and silencing capacity. Recently, we developed a polysorbitol-based osmotically active transporter (PSOAT), which exhibits several interesting mechanisms to accelerate gene delivery into cells. Herein, we report the efficacy of using the PSOAT system for small interfering RNA (siRNA) delivery and its specific mechanism for cellular uptake to accelerate targeted gene silencing. We found that PSOAT functioned via a caveolae-mediated uptake mechanism due to hyperosmotic activity of the transporter. Moreover, this selective caveolae-mediated endocytosis of the polyplexes (PSOAT/siRNA) was regulated coincidently with the expression of caveolin (Cav)-1 and cyclooxygenase (COX)-2. Interestingly, COX-2 expression decreased dramatically over time due to degradation by the constant expression of Cav-1, as confirmed by high COX-2 expression after the inhibition of Cav-1, suggesting that PSOAT-mediated induction of Cav-1 directly influenced the selective caveolae-mediated endocytosis of the polyplexes. Furthermore, COX-2 expression was involved in the initial phase for rapid caveolae endocytic uptake of the particles synergistically with Cav-1, resulting in accelerated PSOAT-mediated target gene silencing
Lactobacillus plantarum Lipoteichoic Acid Inhibits Oral Multispecies Biofilm
No full textIntroduction: Apical periodontitis is an inflammatory disease in the periradicular region of teeth that results from infection by multispecies bacterial biofilm residing in the root canal system. In this study, we investigated whether Lactobacillus plantarum lipoteichoic acid (Lp.LTA) could inhibit multispecies oral pathogenic bacterial biofilm formation. Methods: Highly pure and structurally intact Lp.LTA was purified from L. plantarum. Actinomyces naeslundii, Lactobacillus salivarius, Streptococcus mutans, and Enterococcus faecalis were co-cultured to form oral multispecies biofilm in the presence or absence of Lp.LTA on culture plates or human dentin slices. Preformed biofilm was treated with or without Lp.LTA, followed by additional treatment with intracanal medicaments such as calcium hydroxide or chlorhexidine digluconate. Confocal microscopy and crystal violet assay were performed to determine biofilm formation. Biofilm on human dentin slices was visualized with a scanning electron microscope. Results: Biofilm formation of multispecies bacteria on the culture dishes was dose-dependently reduced by Lp.LTA compared with the nontreatment control group. Lp.LTA also inhibited multispecies biofilm formation on the dentin slices in a dose-dependent manner. Interestingly, Lp.LTA was shown to reduce preformed multispecies biofilm compared with the nontreatment group. Moreover, Lp.LTA potentiated the effectiveness of the intracanal medicaments in the removal of preformed multispecies biofilm. Conclusions: These results suggest that Lp.LTA is a potential anti-biofilm agent for treatment or prevention of oral infectious disease, including apical periodontitis, which is mainly caused by multispecies bacterial biofilm.OAIID:RECH_ACHV_DSTSH_NO:T201825186RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A076889CITE_RATE:2.886DEPT_NM:치의학과EMAIL:[email protected]_YN:YN
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