Min Ju Kim;Joon Hurh;Ha-Rim Kim;Sang-Wang Lee;Hong-Sig Sin;Sang-Jun Kim;Eun-mi Noh;Boung-Jun Oh;Seon-Young Kim
Journal of Microbiology and Biotechnology
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제33권4호
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pp.463-470
/
2023
This study confirmed the change in functional composition and alcohol-induced acute liver injury in Aloe arborescens after fermentation. An acute liver injury was induced by administration of ethanol (3 g/kg/day) to C57BL/6J mice for 5 days. A fermented A. arborescens Miller leaf (FAAL) extract was orally administered 30 minutes before ethanol treatment. After fermentation, the emodin content was approximately 13 times higher than that of the raw material. FAAL extract significantly attenuated ethanol-induced aspartate aminotransferase, alanine aminotransferase, and triglyceride increases in serum and liver tissue. Histological analysis revealed that FAAL extract inhibits inflammatory cell infiltration and fat accumulation in liver tissues. The cytochrome P450 2E1, superoxide dismutase, and glutathione (GSH), which involved in alcohol-induced oxidative stress, were effectively regulated by FAAL extract in serum and liver tissues, except for GSH. FAAL also maintained the antioxidant defense system by upregulating heme oxygenase 1 and nuclear factor erythroid 2-related factor 2 protein expression. In addition, FAAL extract inhibited the decrease in alcohol dehydrogenase and aldehyde dehydrogenase activity, which promoted alcohol metabolism and prevented the activation of inflammatory response. Our results suggest that FAAL could be used as a potential therapeutic agent for ethanol-induced acute liver injury.
Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.
Objectives: This study tested the hypothesis that cryotherapy duration influences lipopolysaccharide (LPS)-induced inflammation in a rat model. Materials and Methods: Six Wistar rats (Rattus norvegicus albinus) were used. Five sites were selected per animal and divided into 5 groups: a negative control group (NC), 2 positive control groups (PC1 and PC2), and 2 experimental groups (E1 and E2). Cryotherapy was applied for 1 minute (E1) or 5 minutes (E2). An acute inflammatory response was induced in the PC and E groups via subcutaneous administration of 0.5 mL/kg. In the PC2 group, a catheter was inserted without additional treatment. For the E1 and E2 groups, 2.5℃ saline solution was administered through the implanted catheters for 1 and 5 minutes, respectively. The rats were sacrificed, and samples were obtained and processed for histological analysis, specifically examining the presence of polymorphonuclear neutrophils and hemorrhage. The χ2 test was used to compare the presence of acute inflammation across groups. Dependent variables were compared using the linear-by-linear association test. Results: Inflammation and hemorrhage varied significantly among the groups (p = 0.001). A significantly higher degree of acute inflammation was detected (p = 0.0002) in the PC and E1 samples than in the E2 group, in which cryotherapy was administered for 5 minutes. The PC and E1 groups also exhibited significantly greater numbers of neutrophils (p = 0.007), which were essentially absent in both the NC and E2 groups. Conclusions: Cryotherapy administration for 5 minutes reduced the acute inflammation associated with LPS and catheter implantation.
Haiyan Xiang;Yun Zhang;Yan Wu;Yaling Xu;Yuanhao Hong
The Korean Journal of Physiology and Pharmacology
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제28권1호
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pp.11-19
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2024
Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.
Purpose: The aim of this study was to investigate the efficacy of photo-crosslinked gelatin methacryloyl (GelMa) hydrogel containing calcium phosphate nanoparticles (CNp) when applying different fabrication methods for bone regeneration. Methods: Four circular defects were created in the calvaria of 10 rabbits. Each defect was randomly allocated to the following study groups: 1) the sham control group, 2) the GelMa group (defect filled with crosslinked GelMa hydrogel), 3) the CNp-GelMa group (GelMa hydrogel crosslinked with nanoparticles), and 4) the CNp+GelMa group (crosslinked GelMa loaded with nanoparticles). At 2, 4, and 8 weeks, samples were harvested, and histological and micro-computed tomography analyses were performed. Results: Histomorphometric analysis showed that the CNp-GelMa and CNp+GelMa groups at 2 weeks had significantly greater total augmented areas than the control group (P<0.05). The greatest new bone area was observed in the CNp-GelMa group, but without statistical significance (P>0.05). Crosslinked GelMa hydrogel with nanoparticles exhibited good biocompatibility with a minimal inflammatory reaction. Conclusions: There was no difference in the efficacy of bone regeneration according to the synthesized method of photo-crosslinked GelMa hydrogel with nanoparticles. However, these materials could remain within a bone defect up to 2 weeks and showed good biocompatibility with little inflammatory response. Further improvement in mechanical properties and resistance to enzymatic degradation would be needed for the clinical application.
Objective : We have currently changed treatment strategies to methotrexate(MTX)-based preirradiation chemotherapy with subsequent planned radiation for the initial therapy of primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the results of treating PCNSL with chemotherapy plus radiotherapy (CRT) or radiotherapy(RT) alone. Method and Material : This study involved 10 females and 3 males patients with a mean age of 54.2 years. All patients underwent surgery, open(8 cases) or stereotactic biopsy(5 cases) for histological diagnosis. Eleven tumors were diffuse large B-cell lymphomas. Tumor volume change in the follow-up images and survival time were evaluated in patients treated with CRT and RT alone. In the beginning, two patients received ProMACE-Cytabom chemotherapeutic regimen, but did not complete the course and died of progressive tumor 8 and 9 months after diagnosis, respectively. One patient died at 6 months before chemotherapy. These three were excluded from the survival analysis. Five patients(RT group) completed full courses of cranial irradiation with or without boost. For the current combined modality treatment, high-dose MTXbased chemotherapy(systemic and intrathecal MTX, IV vincristine, and oral procarbazine) followed by whole brain irrdiation to 45Gy to tumor was introduced in 5 patients of CRT group. Result : A complete response was achieved in three of five who received RT only and in all of five who received CRT. All patients in CRT groups are in disease free status at a mean 23 months following therapy. The RT group patients refused any additional salvage therapy at tumor relapse and survived at mean 20 months from diagnosis. The Karnofsky performance status improved in eight of ten patients with treatment. The treatment toxicity included leukoencephalopathy in RT group and severe leukopenia, transient hepatitis, avascular necrosis of femoral head, hearing loss, and amenorrhea in CRT group, respectively. Conclusion : The combined modality therapy of MTX-based chemotherapy plus radiotherapy for PCNSL may enhance tumor response and improve patient survival. The patients who received CRT should be carefully followed up because of the higher risk of treatment-induced late neurotoxicity.
Purpose: In this study, we aimed to evaluate the effects of sex-based non-small cell lung cancer (NSCLC) varieties on survival rates. Materials and Methods: A retrospective study was performed in patients with NSCLC who were diagnosed by histological methods between the years 2000 and 2010. A chi-square test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Of the 844 patients, 117 (13.9%) were women and 727 (86.1%) were men. Adenocarcinoma was more common in women than in men (p<0.0001). There were more women non-smokers than men (p<0.0001). There was no statistically significant difference in ECOG PS, weight loss>10%, stage, LDH, albumin and treatment between women and men. Women younger than 65 years (17.0 vs 12.0 months; p=0.03), who had adenocarcinoma histology (15.0 vs 10.0 months; p=0.006) and who had a hemoglobin level ${\geq}12g/dL$ (18.0 vs 12.0 months; p=0.01) were found to have a better median OS rate than men. Median OS rates were found to be 13.0 months in females and 12.0 months in males (p=0.14). Among metastatic patients, the median OS was 11.0 months in females and 8.0 months in males (p=0.005). Among stage IIIB and stage IV patients who had first line platinum-based chemotherapy, the median OS was 17.0 months in women and 11.0 months in men (p=0.002). The response rate of chemotherapy was higher in women than in men (p=0.03). Conclusions: In our study, we found that survival duration is longer and chemotherapy response is better in women with NSCLC who do not have anemia or comorbidities and who are mostly non-smokers with adenocarcinomas. Further studies regarding the causes of these differences may provide clarity on this subject.
Obstructive sialadenitis of major salivary glands is a common entity that occurs either in sialolithiasis or in foreign-body obstruction of the excretory ducts. This is characterized histologically by the presence of duct-like structural groups in a highly fibrotic stroma. Although the pathologic features are well recognized, the various cell types involved in the atrophy and subsequent regeneration of the obstructed salivary gland have been controversial. For this reason, an animal model of obstructive sialadenitis that induced atrophy in the salivary gland was used. Experimental study was performed to observe changes of submandibular gland in rabbit and apply the results to clinical activity. Forty-five rabbits each weighing about 3Kg were used and divided into control and experimental group. In the experimental group, ducts of submandibular gland was ligated and cutted divided into each twenty rabbits. Rabbits were serially sacrificed on the 3rd, 5th, 14th, 30th day of experiment. The submandibular glands were dissected out at sacrifice and stained with H&E, MT, immunohistochemical stain and the histological examinations were carried out under the light and transmission electron microscope. After examination and comparison of all specimens, the results of this study were as follows: 1. In the features of H&E stain, moderate infiltration of inflammatory cell were present at 3rd day of experiment. The features of ductal metaplasia was observed after 7th day in the ligation group and destructive changes was continued. In the cutting group, atrophic changes were less severe than ligation group but the small ductule were separated from stroma after 7th day. 2. In the feature of MT stain, apposition of connective tissue was increased in all group, more active in ligation group. 3. In the features of immunohistochemical stain, ligation group showed increased PCNA positive response at 7th day and the higher activity of duct cells was observed. Severance group showed more PCNA positive response than ligation group at 30th day. 4. In TEM features, ductal metaplasia was started at 7th day and degenerative change with margination of nucleus had been severe. Although ductal metaplasia was seen in the severance group, more numerous granule in different size was founded than ligation group. From above results, degenerative change was identified with ductal metaplasia, apically apposition of granule, r-ER destruction in ligation group. Severance of duct elicit degenerative change of grandular cells but the change was less severe than ligation group and more PCNA positive cell was founded at acinar cell.
The water extract of Dohongsamul-Tang(DHSMT) has been traditionally used to stroke and brain injuries in Oriental Medicine. The present study was designed to investigate the effects of DHSMT on the gene expression profile of cerebral infarction by cDNA microarray in photothrombotic ischemia mouse model. Photothrombotic ischemia was induced in stereotactically held male BALB/c mice using rose bengal and cold light. MRI was performed 24 hours after inducing photothrombosis using 1.5 T MRI and 47 mm surface coil to obtain T2-weighted, and contrast-enhanced images. After MRI test, animal was sacrificed and the brain sections were stained for hematoxylin and eosin and immunohistochemistry. MRI and histological analysis revealed that lesion of thrombotic ischemia was well induced in the cortex with the evidence of biological courses of infarction. The target area of thrombotic infarction was 1 mm anterior to bregma and 3 mm lateral to midline with 2 mm in diameter, which were decreased by administration of DHSMT. To assess gene expression pattern of cerebral infarction, mRNA was isolated and reacted with microarray chip(Agilant's DNA Microarray 44K). Scatter and MA plot analysis were performed to clustering of each functional genes. M value [M=log2(R/G), A={log2(R ${\times}$ G)}/2] was between -0.5 and +0.5 with 40% difference. After pretreatment with DHSMT, the expression levels of mRNA of many genes involved in various signaling pathway such as apoptosis, cell cycle, cell proliferation, response to oxidative stress, immune response, angiogenesis, and inflammatory cytokine were markedly inhibited in photothrombotic ischemia lesion compared to the control group. These results suggest that DHSMT prevent ischemic death of brain on photothrombotic ischemia model of mice through modulation of gene expression at the transcriptional level.
This study was performed to assess the efficacy of high voltage pulsed galvanic current for the healing of wounds in rabbits. Skin wounds were created laterally on the flank of 12 domestic rabbits($3{\times}3cm$). The wounds of each group were treated with an intensity of 170 V at a frequency of 70 pulses per second, which was applied for 30 minutes a day for 10 days. The experimental groups were randomly assigned to either EXP I (n=3), EXP II(n=3), EXP III(n=3) or control(n=3). Each group was stimulated under the following conditions : 1) EXP I (Negative polarity), 2) EXP II (Change in polarity, negative electrode stimulation during the first 3 days and then positive electrode stimulation from 4 to 10 days), 3) EXP III(Positive polarity), 4) control(No stimulation). An active electrode was placed over the wound and a dispersive electrode on the buttock. The rate of wound closure was compared with the original wound size, evaluated by a tracing film in each measurement period. Finally, on the wound in each group, skin tissue was excised for histological evaluation after treatment for 10 days. The results obtained are as follows : 1) It was found that the control group did not show a complete remodeling of epitherial layer and had a chronic inflammatory response. Judging from the irregularity of intercellular space and the loose alignment of connective tissue, these findings show that wound healing was delayed. 2) EXP I showed a significant bactericidal effect, but a moderate response of vasodilation. The rate of wound closure was slower when compared with EXP II, III. 3) EXP II showed a complete remodeling of epitherial layer and a positive repair of connective tissue. Its rate of wound closure was best when compared with the others. 4) EXP III had a slower rate of wound closure than EXP II, but judging from the greater proliferation of collagen fibers and the dense alignment of connective tissue, this positive electrode was very effective in the formation of neo - connective tissue.
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