Juhyun Lee;Ji-Won Park;Jinseon Choi;Seok Han Yun;Bong Hyo Rhee;Hyeon Jeong Jeong;Hyueyun Kim;Kihoon Lee;Kyung-Seop Ahn;Hye-Gwang Jeong;Jae-Won Lee
Biomolecules & Therapeutics
/
v.32
no.5
/
pp.546-555
/
2024
Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid and inducible nitric oxide synthase/cyclooxygenase-2/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of ALI mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1/ NAD(P)H quinone dehydrogenase 1 in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.
Man Lu;Liwei Xie;Sijie Yin;Jing Zhou;Lingmei Yi;Ling Ye
Journal of Microbiology and Biotechnology
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v.34
no.9
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pp.1769-1777
/
2024
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect related to activation of substance P (SP). SP activation can result from dysregulation of the gut-brain axis, and also from activation of protein kinase A signaling (PKA) signaling. In this study, we connected these factors in an attempt to unveil the mechanisms underlying CINV and develop new therapeutic strategies. Female rats were injected with cisplatin (Cis) to induce pica. Fecal samples were collected before/after injection, and subjected to lipid metabolomics analysis. In another portion of pica rats, the PKA inhibitor KT5720 was applied to investigate the involvement of PKA signaling in CINV, while fecal microbiota transplantation (FMT) was implemented to verify the therapeutic effect of the lipid metabolite 14(15)-EpETE. Pica symptoms were recorded, followed by ileal histological examination. The targeting relationship between 14(15)-EpETE and glucagon was determined by bioinformatics. SP and glucagon/PKA signaling in rat ileum, serum, and/or brain substantia nigra were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and/or western blot. The results showed a significantly lower level of 14(15)-EpETE in rat feces after Cis injection. KT5720 treatment alleviated Cis-induced pica symptoms, ileal injury, SP content increase in the ileum, serum, and brain substantia nigra, and ileal PKA activation in rats. The ileal level of glucagon was elevated by Cis in rats. FMT exerted an effect similar to that of KT5720 treatment, relieving the Cis-induced changes, including ileal glucagon/PKA activation in rats. Our findings demonstrate that FMT restores 14(15)-EpETE production, which inhibits SP release by targeting GCG/PKA signaling, ultimately mitigating CINV.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by both genetic and environmental factors. Fludarabine is a selective inhibitor of signal transducer and activator of transcription 1 (STAT1). Recently, STAT1 inhibitors have been considered potential treatments for SLE, due to the relationship between its pathogenesis and STAT1 pathway-mediated cytokines such as interferons. In the current study, we evaluated the therapeutic effects of fludarabine in an SLE animal model and explored its effects on T cell responses. 12-week-old C57BL/6 mice with topically administered R848 exhibited lupus-like phenotypes. Disease activity, such as proteinuria, autoantibody levels, immunoglobulin titers, the histological score, and C3 deposition, greatly improved with fludarabine treatment. In addition, fludarabine inhibited CD4+ T cells and T helper 1 (Th1) cells in the spleen and significantly decreased the differentiation of Th1 cells in vitro. These results indicate that Th1 cells play a critical role in the pathogenesis of lupus nephritis (LN). Thus, fludarabine exerted therapeutic effects on lupus animal models by suppressing Th1 cells via STAT1 inhibition. We propose that targeting STAT1 signaling using fludarabine could be an effective therapy for treating LN.
Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.
The study was conducted to find out the concentrations of sex hormones and the contents of metabolites in serum, and the changes of weights and tissues on ovary, thyroid gland and adrenal gland according to gestation period in rabbit. The results were summarized as follows: 1. The ovary weights were increased significantly with the time e lapse after gestation and recovered normally at 5 days after parturition. In the histological changes of ovary, the lutein cells were hypertrophied and the secretory granules were increased actively until 3 weeks after gestation, and then a trophied thereafter. 2. The thyroid gland weights at all observation times were higher than those in control group, and the significance was recognized at 1, 3 and 4 weeks after gestation. The histological features of the secretory epithelium were the hyper trophic and columnar condition stimulating the functional state from 1 week after gestation. 3. The adrenal gland weights in experimental group were recognized significantly at 4 weeks after gestation, but showed higher than those in control group at all observation times. The zona fasciculata and zona reticularis of the gland showed the slight hypertrophic condition, but the zona glomeerulosa and adrenal medulla did not find out any particular changes. 4. The serum concentrations of progesterone and LH reached a peak level at 2 weeks and 1 week after geestation respectively, and rapidly began to decline thereafter. 5. The serum concentrations of estradiol-$17{\beta}$ and FSH were not detected below 20.0 pg/ml and 1.3 mIU/ml respectively. 6. The contents of total protein and non-protein nitrogen nitrogen were decreased gradually with the time elapse after gestation, but the significant differences were recognized from 3 weeks. 7. The total lipids were not changed markedly until 3 weeks, but increased significantly at 4 weeks after gestation and at 5 days after parturition. 8. The serum cholesterol tended to be decreased until 3 weeks, but increased at 4 weeks after gestation and at 5 days after parturition. 9. The serum calcium showed a continuous decrease during the gestation period, but the significant differences were recognized at 3 and 4 weeks. The serum phosphorus also had a significant decrease at 4 weeks after gestation.
Purpose: The purpose of this study is to evaluate the clinical, radiological and histopathological results after microfracture surgery for degenerative arthritis of the knee. Materials and Methods: From Oct. 1997 to Dec. 1998, 48 knees in 46 patients were treated by microfracture technique. Their mean age at the time of operation was 56 years(range, 40-75 years) and mean period of follow-up study was one year(range, 7-20 months). For 24 knees in 22 patients, 'second-look' arthroscopies and biopsies were performed at 6 months following microfracture. At the last follow up clinical results were evaluated with Baumgaertner's scale. The specimens of 24 cases were stained with H-E, Safranin-O, and Masson's trichrome. Eighteen of 24 cases were stained immunohistochemically and the Western blotting test was performed on 12 cases for type II collagen. We analyzed the relationship of the Western blotting for type II collagen with clinical score, preoperative varus deformity, joint space widening in radiological result, extent of repaired articular cartilage in '2nd-look' arthroscopic findings, patient's age and weight. Results: Clinical results were excellent in 90% and good in 10%. Among the 24 knees, more than 80% of areas of chondral defect were covered with regenerated cartilage in 21 knees Histologically, the repaired tissue appears to be a hybrid of hyaline cartilage and fibrocartilage. Repaired cartilage contains variable amounts of type II collagen with immunohistochemical staining. The results of the Western blotting test were similar. The amounts of type II collagen formation had positive correlation with the extent of repaired cartilage and preoperative varus deformity. Conclusion: 'Second-look' showed that the chondral defect areas were covered with newly grown grayish white tissue. Articular cartilage repair was confirmed with histological and immunohisto-chemical study qualitatively, and the amount of type II collagen was calculated with the Western blotting test quantitatively. The exact nature and fate of repaired cartilagenous tissues need further long term follow-up study. The results of this study provide the rationale to select osteoarthritic patients indicated for microfracture surgery.
This study was performed using animals to confirm the effect of tourmaline-ionized water (TIW) the properties of which were changed by tourmaline energy and electric discharge. In the ICR mice fed high-fat diet, body weight increasing rate of the TIW-treated group (Exp) was generally decreased and moreover exhibited significance at 11th week (P<0.05) compared with the control (Con) group fed distilled water, although water intake of the Exp group was lower than that of the Con group. In the ICR mice with $CCl_4$-induced hepatotoxicity, AST and ALT activities of the Exp group were not significant but showed some decreasing trend, and histological damage of liver was less compared with thatof the Con group. On the study of ethanol-induced hangovers in Sprague-Dawley rat, blood alcohol concentration was significantly decreased (P<0.01), activity of GST, antioxidant enzyme related to the alcohol metabolism, was increased in liver tissue (P<0.05), and AST and ALT show a tendency to be decreasedin the Exp group. These results suggest that drinking TIWhas not only some obesity preventing effect but also an alcohol detoxification effect and liver protecting effect in vivo. It is supposed due to a structural change of water cluster and a property which maintains the changed structure through tourmaline energy and electric discharge. Therefore, TIW has a potentiality to be developed as functional water with several beneficial effects as well as for daily drinking, but further study on the mechanism related with efficacy will be necessary.
Since 1959 ${\beta}-aminoethylphosphonic$ acid was discovered in the living organism, the biosynthesis and biological functions of aminophosphonic acids have been extensively studied. The author designed and carried out this study for 14 weeks to find out the metabolic function of Ethylaminophosphonic acid (AEP) and it's utilization in the living body. Sixty rats, thirty males and thirty females aged $40{\pm}5$ days were divided into two parts, one for alanine supplemented as control group and the other for AEP as experimental group to compare metabolic pathway of ordinary amino acid with that of AEP. Both alamine and AEP group were divived into two subgroups according to the level of supplements, 0.1% and 0.2% of the diet. The major components of the diet in this study were composed of 20% casein, 72% Sugar, 4% fat, 4% salt Mixture, and all kind of Uitamins in adeguate amount. For comparision of biological values between experimental and control group in terms of body weight, uninary nitrogen, creatinine excretion and final orgam weight, there were no statically significant difference in these respects. This meant AEP could be utilized in the body as much as alanine could. Urinary phosphorus excretion was determined by developing the blue color to read on the Spectronic 20. Statistically insignificance in the urinary phosphorus excretion between experimental and control group was observed in spite of the supplementation of phosphorus of AEP for experimental group in the diet. The level of blood phosphorus was higher in experimental group than that in control group this result supported above result. In the analysis of fat and nitrogen contents in the liver, AEP group showed slightly higher than control in both respects. But it was noteworthy 0.2% AEP group in both sex were higher than 0.1% AEP in liver fat content. Histological examinal of internal organs liiver, lung, spleen, heart, kindey, adrenal and sex organs showed no changes in all groups included in this study. The group supplemented higher level of diet. by alanine 0.2% and AEP 0.2% stayed on less body weight gain and lower liver weight. This result could be interpreted that amino acid imbalanced condition was arose in the body.
Radiation therapy for lung cancer is an effective treatment during monotherapy or combination therapy. Studies have reported that the optimum utilization rate of radiation therapy is estimated at 61% to 74%. Radiation therapy in Korea has been investigated to be low; further studies are needed. This study was intended to assess the appropriateness of the use of radiation and to reveal the use of radiation therapy-related factors by examining radiation therapy in lung cancer patients of Busan and South Gyeongnam Province. This study was aimed at the population diagnosed with lung cancer in Busan and South Gyeongnam Province. To conduct the study, 1036 patients enrolled in two hospitals were collected and 897 appropriate as subjects were selected. We compared the optimum utilization rate and actual rate of radiation therapy, and revealed the adequacy and related factors for use of radiotherapy. Of 897 patients, 503 (56%) were treated with medical therapy and 394 (44%) were given radiotherapy. The radiotherapy utilization rate of all lung cancer patients was 42%. The proportion of non-small cell lung cancer by histologic type was 33% and that of small cell lung cancer was 90%. Factors related to radiation therapy used in cancer were age, histological type, clinical stage, doctor refereed to, and clinical examination. Compared to radiation utilization by region (site), curative chest therapy was 42%; palliative treatment was 26%. In the comparison of histologic types, utilization of small-cell lung cancer is lower; the lowest especially in the stage III. Utilization of radiation therapy in Busan and South Gyeongnam Province was lower than the reasonable one. Utilization difference could be explained by patient factors, tumor factors, and health service factors. To improve utilization,development ofoutreach service programs and activation of the multidisciplinary team are required.
This study was conducted to investigate the reproductive ecology of the Korean Mandarin Fish, Siniperca scherzeri in Seomjin River and Imjin River from April to October 2008. After have investigating the relationship between standard length (SL) and Gonadosomatic index (GSI) of Siniperca scherzeri, we can conclude that the body length of maturation was over 200mm SL in case of females and over 180mm SL in males. The GSI of the females that were from Seomjin river was the highest in April (7.43%), and gradually decreased after May (5.55%) and June (3.58%). The GSI was decreased sharply in August and indicated the lowest value in September (0.44%). The GSI of the females that were from Imjin river showed similar tendency of females' GSI from Seomjin river. The GSI of males from Imjin river was totally higher than that of females, it was 5.96% in April, and 8.03% in May. It was lowered in early June, and late June, it indicated 2.12%. In September, it was the lowest value (0.20%), and increased after October (0.54%). The result of histological study of ovary presented similar result of the study of GSI in Seomjin river and Imjin river. The ratio that fishes constitute in stomach contents of Siniperca scherzeri was 92% in Seomjin river and 90% in Imjin river. Digestion of food organisms and the ratio of unidentifiable fishes in stomach contents was fairly high, and it was 50% in Seomjin river and 72.2% in Imjin river. In the period of study, eating ratio was very low 38.3% (36 ind.) in Seomjin river and 21.8 (53 ind.) in Imjin river.
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