This review discusses the cellular and molecular mechanisms by which the endometrial estrogen and progesterone receptors regulate local estrogen production, expression of the specific estrogen receptors, progesterone resistance, inflammatory responses and the differentiation and survival of endometriotic cells in endometrial inflammation. The epigenetic aberrations of endometrial stromal cells play an important role in the pathogenesis and progression of endometriosis. In particular, differential methylation of the estrogen receptor genes changes in the stromal cells the dominancy of estrogen receptor from ERα into ERβ, and results in the abnormal estrogen responses including inflammation, progesterone resistance and the disturbance of retinoid synthesis. These stromal cells also stimulate local estrogen production in response to PGE2 and the SF-1 mediated induction of steroidogenic enzyme expression, and the increased estradiol then feeds back into the ERβ to repeat the vicious inflammatory cycle through the activation of COX-2. In addition, high levels of ERβ expression may also change the chromatin structure of endometrial mesenchymal stem cells, and together with the repeated menstrual cycles can induce formation of the endometriotic tissue. The cascade of these serial events then leads to cell adhesion, angiogenesis and survival of the differentiation-disregulated stromal cells through the action of inflammatory factors such as ERβ-mediated estrogen, TNF-α and TGF-β1. Therefore, understanding of the dynamic hormonal changes during the menstrual cycle and the corresponding signal transduction mechanisms of the related nuclear receptors in endometrium would provide new insights for treating inflammatory diseases such as the endometriosis.
Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ∆BspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucella at the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions: BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.
Sohyeong Oh;Donggeun Yoo;Kim Myeonghwan;Park Jiyong;Choi Yeongjin;Kwonpil Park
Korean Chemical Engineering Research
/
v.61
no.4
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pp.517-522
/
2023
A chemical/mechanical durability test of polymer membrane evaluation method is used in which air and hydrogen are supplied to the proton exchange membrane fuel cell (PEMFC) and wet/dry is repeated in the open circuit voltage (OCV) state. In this protocol, when wet/dry is repeated, voltage increase/decrease is repeated, resulting in electrode degradation. When the membrane durability is excellent, the number of voltage changes increases and the evaluation is terminated due to electrode degradation, which may cause a problem that the original purpose of membrane durability evaluation cannot be performed. In this study, the same protocol as the department of energy (DOE) was used, but oxygen was used instead of air as the cathode gas, and the wet/dry time and flow rate were also increased to increase the chemical/mechanical degradation rate of the membrane, thereby shortening the durability evaluation time of the membrane to improve these problems. The durability test of the Nafion 211 membrane electrode assembly (MEA) was completed after 2,300 cycles by increasing the acceleration by 2.6 times using oxygen instead of air. This protocol also accelerated degradation of the membrane and accelerated degradation of the electrode catalyst, which also had the advantage of simultaneously evaluating the durability of the membrane and the electrode.
Sohyeong Oh;Yuhan Han;Donggeun Yoo;Myoung Hwan Kim;Ji Young Park;Youngjin Choi;Kwonpil Park
Korean Chemical Engineering Research
/
v.62
no.1
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pp.7-12
/
2024
The durability of the catalyst support has a significant effect on the durability of proton exchange membrane fuel cells (PEMFC). The accelerated durability evaluation of the catalyst support is performed at a high voltage (1.0 to 1.5 V), and the catalyst and ionomer binder in the catalyst layer are also deteriorated, hindering the evaluation of the durability of the support. The existing protocol (DOE protocol) was improved to find conditions in which the support, which is a durability evaluation target, deteriorates further. A protocol (MDOE) was developed in which the relative humidity was lowered by 35% and the number of voltage changes was reduced. After repeating the 1.0 ↔ 1.5 V voltage change cycle, the catalyst mass activitiy (MA), electrochemical active area (ECSA), electrical double layer capacity (DLC), Pt dissolution and particle growth were analyzed. Reaching 40% reduction in mass activity, the MDOE protocol took only 500 cycles, reducing the number of voltage changes compared to the DOE method and increasing the degradation of the carbon support by 50% compared to the DOE protocol.
$\underline{Purpose}$: To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. $\underline{Materials\;and\;Methods}$: Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total $55.4{\sim}64.8$ (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over $7{\sim}8$ weeks. 50 or $60\;mg/m^2$ of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel $135\;mg/m^2$ and cisplatin $75\;mg/m^2$ was administered every 3 weeks. $\underline{Results}$: Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. $\underline{Conclusion}$: Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity rate. But local failure occurred frequently after the remission and large tumor size was a poor prognostic factor. Further investigations are needed to improve the local control.
$\underline{Purpose}$: Combined modality therapy including chemotherapy, surgery and radiotherapy is considered the standard of care for the treatment of stage III non-small cell lung cancer (NSCLC). This study was conducted to evaluate the efficacy of paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC. $\underline{Materials\;and\;Methods}$: Between July 2000 and October 2005, thirty-nine patients with stage IIIB NSCLC were treated with two cycles of induction chemotherapy followed by concurrent chemoradiotherapy. The induction chemotherapy included the administration of paclitaxel ($175\;mg/m^2$) by intravenous infusion on day 1 and treatment with cisplatin ($75\;mg/m^2$) by intravenous infusion on day 1 every 3 weeks. Concurrent chemoradiotherapy included the use of paclitaxel ($60\;mg/m^2$) plus cisplatin ($25\;mg/m^2$) given intravenously for 6 weeks on day 43, 50, 57, 71, 78 and 85. Thoracic radiotherapy was delivered with 1.8 Gy daily fractions to a total dose of $54{\sim}59.4\;Gy$ in $6{\sim}7$ weeks (median: 59.4 Gy). $\underline{Results}$: The follow up period was $6{\sim}63$ months (median: 21 months). After the induction of chemotherapy, 41.0% (16 patients) showed a partial response and 59.0% (23 patients) had stable disease. After concurrent chemoradiotherapy, 10.3% (4 patients) had a complete response, 41.0% (16 patients) had a partial response, and the overall response rate was 51.3% (20 patients). The 1-, 2-, 3-year overall survival rates were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The 1-, 2-, 3-year progression free survival rates were 43.6%, 24.6%, and 24.6%, respectively, with median progression free survival time of 10.7 months. Induction chemotherapy was well tolerated. Among 39 patients who completed the entire treatment including chemoradiotherapy, 46.3% (18 patients) had esophagitis greater than grade 3 and 28.2% (11 patients) had radiation pneumonitis greater than grade 3. $\underline{Conclusion}$: Paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC seems to be an effective treatment. Occurrence of esophagitis and pneumonitis represents a significant morbidity and suggests a modification of the treatment regimen, either with the chemotherapy schedule or with radiotherapy treatment planning.
Purpose: The effect of concurrent chemoradiotherapy was analyzed in elderly patients when used in the treatment of locally advanced esophageal cancer. Materials and Methods: The retrospective analysis included 28 elderly patients aged 65 or older, with histopathologically confirmed squamous cell carcinoma of the esophagus, underwent concurrent chemoradiotherapy from January 2001 to July 2007. The squamous cell carcinoma disease stages included 8 patients (28.8%) in stage IIa, 10 patients (35.7%) in stage IIb, and 10 patients (35.7%) in stage III. Fractionated radiotherapy was performed with a 6 MV or 10 MV X-ray for 45~63 Gy (median: 59.4 Gy). Chemotherapy was applied concurrently with the initiation of radiotherapy. A 75 mg/$m^2$ dose of Cisplatin was intravenously administered on day 1. Further, 5-FU 1,000 mg/$m^2$ was continuously administered intravenously from days 1 to 4. This regimen was performed twice at 3-week intervals during radiotherapy. Two cycles of consolidation chemotherapy was performed after radiotherapy. Results: The follow-up period was 3~72 months (median: 19 months). The treatment responses after concurrent chemoradiotherapy included a complete response in 11 patients (39.3%), a partial response in 14 patients (50.0%), and no response in 3 patients (10.7%). The overall response rate was 89.3% (25 patients). The overall 1-, 2- and 3-year survival rates were 55.9%, 34.6% and 24.2%, respectively. The median survival time was 15 months. Two-year survival rates of patients with a complete response, partial response, and no response were 46.2%, 33.0%, and 0%, respectively. The stage and tumor response after concurrent chemoradiotherapy were statistically significant prognostic factors related with survival. No treatment-related deaths occurred in this study. Conclusion: Concurrent chemoradiotherapy is a relatively effective treatment without serious complications in elderly patients with locally-advanced esophageal cancer.
This study was carried out to examine the expression of the circadian clock genes in the mouse ovary and testis at different developmental stages. Expression of Period1(Per 1), Period2(Per2), Period3(Per3), Cryptochrome1(Cry1), Cyptochrome2(Cry2), Clock Small and Prokineticin1 and Prokineticin2 receptor(Prok1r, Prok2r) genes in mouse ovary was explored by semiquantitative reverse transcription Polymerase chain reaction(RT-PCR) according to the developmental stage(post partum day; ppd 1, 7, 10, 21 and 35). Immunohistochemistry using PER1 antibody was also analyzed. The differential expression pattern of clock genes was presented according to stages of the mouse ovarian development (ppd 1, 7, 10, 21 and 35). In the cases of ovaries, at the starting point of follicle growth at ppd 7 and 10, the clock gene expression patterns were changed vastly. According to the developmental stages, the clock genes were highly expressed at ppd 7 and 10 in mouse testis also. Receptors for Prok2, the circadian output molecule of SCN, were also expressed in ovary at ppd 7 and in testis at ppd 1 and 7, respectively. Immnunohistochemical analysis of PER1 showed positive signals in the cytoplasm of oocytes and granulosa cells. The level or PER1 expression was increased in cells at the spermatogonia and the condensing spermatids. The expression pattern of Perl and localization of PER1 were showed similar patterns according to the developmental stages in ovary and testis. Taken together, it could be observed that the expression of clock genes was highly correlated with gonadal development and germ cell differentiation in mice. Therefore, in this study, circadian programming of the genes in the ovary and testis is strongly imposed across a wide range of core reproductive cycles and normal development of gametes. Although the existence of circadian genes is clearly investigated, further studies on the direct evidence is required for the understanding of the relationship between circadian genes and regulation of gonadal differentiation and germ cell development.
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.10
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pp.1555-1564
/
2014
This study investigated the effects of combined treatment of immersion liquids (adjusted pH 4.5 with Citrus junos concentrate (CL), pH 5.5 with Prunus mume concentrate (PL), or no pH adjustment, pH 6.5, control) and high hydrostatic pressure (HHP, 450 MPa) on shelf-life and quality of mackerel. In this study, we measured changes in viable cell counts, pH level, volatile basic nitrogen, thiobarbituric acid reactive substances, color analysis, volatile organic compounds, and sensory evaluation of mackerel at $4^{\circ}C$ for 20 days. CL/HHP and PL/HHP treatments reduced viable cell counts by 3 log cycles during storage compared to the control. Mackerel treated with CL/HHP and PL/HHP showed significantly lower TBARS and VBN levels as compared to the control. After combined treatment, lightness and whiteness increased but redness decreased. VOCs tests showed that contents of alcohol, acid, and ketones in mackerel fillet treated with CL/HHP and PL/HHP were relatively reduced. Especially, CL/HHP and PL/HHP suppressed production of sulfur. In the sensory evaluation, aroma, taste, salinity, hardness, and springiness of mackerel treated with combined HHP showed higher scores than the control. These results suggest that immersion liquids and HHP treatments may increase shelf-life of mackerel and maintain quality during storage at $4^{\circ}C$.
Background : Tumor associated antigens, which are produced specifically by tumor cells, are promising targets for the early diagnosis and immunotherapy. Among the tumor associated antigens, MAGE (a melanoma antigen), BAGE, GAGE, PRAME and NY-ESO were named as cancer/testis specific antigens they are detected exclusively in the testis or cancer cells If MAGE is easily detectable in the sputum, it would become a convenient method for diagnosing lung cancer. This study was undertaken to investigate MAGE expression in the induced sputum obtained from lung cancer patients. Materials and Methods : In 14 control patients and 30 lung cancer patients, the induced sputum was collected after inhaling 3% saline(5 cc) delivered by nebulizer for approximately 5 minutes after a mouth rinse and bronchodilator inhalation. The induced sputum was placed in a conservative-mixed solution (guanidinium isothiocyanate, Triton X-100). The total cellular mRNA was extracted from the cells and RT PCR and nested PCR were run in 30 and 35 cycles respectively, with two different types of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results : MAGE expression was not detected in the 14 controls, but in the 30 cancer patients, MAGE was found in 24 patients (80%, p=0.001). In the cancer patients, there were no differences in the expression level according to the tissue types (squamous cell cancer 13/17, adenocarcinoma 7/9, and small cell cancer 4/4, p-0.56). Among the 24 MAGE-positive patients, the tumor was not visible on a bronchoscopy in 11 patients (45.8%). Conclusion : A study of MAGE in induced sputum appears to be a useful and complementary method in the diagnosis of lung cancer. A further prospective study with more patients is recommended.
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