Zhou, Wei;Quan, Juan-Hua;Gao, Fei-Fei;Ismail, Hassan Ahmed Hassan Ahmed;Lee, Young-Ha;Cha, Guang-Ho
Parasites, Hosts and Diseases
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v.56
no.2
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pp.135-145
/
2018
Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.
Purpose : Hypoalbuminemia is a rare cause of pleural effusion. The relationship between the severity of hypoalbuminemia and the clinical course of pleural effusion is unclear. The aim of this study was to evaluate the change of clinical course according to the severity of hypoalbuminemia due to pleural effusion in children. Methods : A total of 96 patients admitted to Pusan National University Hospital with pleural effusion from August 1998 to August 2004 were studied retrospectively. The 79 patients who had only infectious causes were evaluated according to their albumin levels. They were divided into the two groups : group 1 had serum albumin levels of ${\leq}2.5g/dL$; group 2 : >2.5 g/dL. The clinical courses of each group were compared. Results : The nature of pleural effusion was transudates in seven cases and exudates in 89 cases. The most commom causes of transudates were renal failure(four cases) and the most common causes of exudates were parapneumonic effusion(58 cases). There was no statistical significance in mean ages, BUN, creatinine, potassium, bilirubin and WBC in each group. Four patient in group 1 and 26 patients in group 2 improved after medication of antibiotics or anti-tuberculosis agents only. Fourteen patients in group 1 and 26 patients in group 2 improved after thoracostomy with use of antibiotics. Eight patients in group 1 and one patient in group 2 had ventilator care with use of antibiotics therapy. Conclusion : Children who were diagnosed as pleural effusion with low serum albumin levels on admission had poorer prognoses than those with normal levels. We conclude that lower serum albumin level on admission is an important prognosis factor in a patient with pleural effusion.
Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.
Kim, Ju-Ye;Kim, Ji-Hyun;Moon, Soon-Jung;Cho, Byong-Soo;Cha, Sung-Ho
Pediatric Infection and Vaccine
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v.7
no.1
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pp.152-158
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2000
Purpose : Kawasaki disease is an acute illness of unknown cause that affects infants and children. Sometimes, cervical lymphadenitis that seems to be caused by bacterial or viral agents at admission would be changed to Kawasaki disease within several days of hospitalization. Lymphadenopathy is one of major presenting manifestation of both cervical lymphadenitis and Kawasaki disease. We compared Kawasaki disease with cervical lymphadenopathy as the initial manifestation with cervical lymphadenitis without other typical manifestations of Kawasaki disease. Methods : We describe and compare the clinical characteristics of 15 patients with Kawasaki disease which were misdiagnosed as cervical lymphadenitis and 125 patients with cervical lymphadenitis, retrospectively. Results : The clinical characteristics of Kawasaki disease with cervical lymphadenopathy as an initial presenting manifestation were older in age and had more frequent abnormalities in markers of systemic inflammation than kawasaki disease without cervical lymphadenopathy. They would have greater abnormalities in markers of inflammation than cervical lymphadenitis alone. They had higher mean WBC, cESR, CRP which were compared with the patients with cervical lymphadenitis. Usually, patients with cervical lymphadenitis responded to antibiotics promptly, but they did not tend to be responded to antibiotics within 48~72hrs. Conclusion : Patients with Kawasaki disease may initially present with findings that strongly suggest bacterial lymphadenitis with or without other manifestations of Kawasaki disease. If they did not response initial antibiotics administration, they should be closed observed for the possible development of the another signs of Kawasaki disease. Earlier diagnosis of Kawasaki disease can avoid the need for unnecessary procedures and antibiotics and lead to more proper therapy directed at Kawasaki disease.
Kim, Ok Kyung;Yoo, Seon A;Nam, Da-Eun;Kim, Yongjae;Kim, Eun;Jun, Woojin;Hwan, Kwontack;Lee, Jeongmin
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.9
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pp.1317-1324
/
2014
The immune system protects the body against harmful substances and infectious agents. Normally, the body can maintain a state of immune homeostasis. However, failure of immune homeostasis results in severe diseases when the immune system is defective. We investigated the immunomodulatory effect of Curcuma longa L. extract in LP-BM5 MuLV (murine leukemia viruses)-induced murine AIDS (acquired immune deficiency syndrome). Mice were divided into six groups: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 200 mg/kg), CL50 (LP-BM5 MuLV infection+dietary supplement of Curcuma longa L. 20% alcohol extract 50 mg/kg), CL200 (LP-BM5 MuLV infection+dietary supplement of Curcuma longa L. 20% alcohol extract 200 mg/kg), and CL500 (LP-BM5 MuLV infection+dietary supplement of Curcuma longa L. 20% alcohol extract 500 mg/kg). We found that dietary supplementation with Curcuma longa L. 20% alcohol extract inhibited elevation of spleen, lymph node, and liver weights as well as reduction of T- and B-cell proliferation and natural killer cell activity induced by LP-BM5 MuLV infection. Moreover, Curcuma longa L. 20% alcohol extract inhibited Th1 (IL-2, IFN-${\gamma}$)/Th2 (IL-4, IL-10) cytokine imbalance and pro-inflammatory cytokine production. In conclusion, these data suggest that Curcuma longa L. has immunomodulatory effects in LP-BM5 MuLV-induced murine AIDS.
Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the leading infectious diseases to humans. It is urgent to discover novel drug targets for the development of antitubercular agents. The 2-C-methyl-Derythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has been considered as an attractive target for the discovery of novel antibiotics for its essentiality in bacteria and absence in mammals. MEP cytidyltransferase (IspD), the third-step enzyme of the pathway, catalyzes MEP and CTP to form 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) and PPi. In the work, ispD gene from M. tuberculosis H37Rv (MtIspD) was cloned and expressed. With N-terminal fusion of a histidine-tagged sequence, MtIspD could be purified to homogeneity by one-step nickel affinity chromatography. MtIspD exists as a homodimer with an apparent molecular mass of 52 kDa. Enzyme property analysis revealed that MtIspD has high specificity for pyrimidine bases and narrow divalent cation requirements, with maximal activity found in the presence of CTP and $Mg^{2+}$. The turnover number of MtIspD is $3.4 s^{-1}$. The Km for MEP and CTP are 43 and $92{\mu}M$, respectively. Furthermore, MtIspD shows thermal instable above $50^{\circ}C$. Circular dichroism spectra revealed that the alteration of tertiary conformation is closely related with sharp loss of enzyme activity at higher temperature. This study is expected to help better understand the features of IspD and provide useful information for the development of novel antibiotics to treat M. tuberculosis.
We described 4 human infection cases of zoonotic fish-tapeworm, Diphyllobothrium nihonkaiense, identified with morphological and molecular characters and briefly reviewed Chinese cases in consideration of it as an emerging parasitic disease in China. The scolex and mature and gravid proglottids of some cases were seen, a rosette-shaped uterus was observed in the middle of the mature and gravid proglottids, and the diphyllobothriid eggs were yellowish-brown in color and displayed a small knob or abopercular protuberance on the opposite end of a lid-like opening. The average size of the eggs was recorded as $62-67{\times}42-45{\mu}m$. The parasitic materials gathered from 4 human cases were morphologically identified as belonging to the genera Diphyllobothrium and Adenocephalus. The phylogenetic analysis based on the nucleotide sequences of cytochrome c oxidase subunit 1 gene of the etiologic agents confirmed that the 4 cases were D. nihonkaiense infection. The finding of 4 additional D. nihonkaiense cases suggests that D. nihonkaiense might be a major causative species of human diphyllobothriasis in China. A combined morphological and molecular analysis is the main method to confirm D. nihonkaiense infection.
Purpose: The multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) test developed recently can help detect enteric pathogens of acute gastroenteritis (AGE). This study aimed to investigate the epidemiology of pathogens in children with AGE using the multiplex RT-PCR. Methods: From May 2015 to June 2018, multiplex RT-PCR tests were performed to identify pathogens in the feces of pediatric patients diagnosed with AGE at a secondary hospital in Seoul, Korea. Results: Of the 1,366 stool samples examined for viral pathogens, 483 (35.3%) tested positive for ≥1 pathogen. Group A rotavirus (RV) was detected in 106 cases (7.8%). The positivity rate increased annually from 3.0% (8/263) to 16.7% (48/288) and surged in 2018 (P<0.001). Norovirus (NoV) GII was the most common viral pathogen (263/1,366, 19.3%), and the positivity rate did not increase during the 3 years. Of the 304 stool samples tested for bacterial pathogens, Campylobacter spp. was the most common bacterial pathogen (32/304, 10.5%), followed by Clostridium difficile (22/304, 7.2%) and Salmonella spp. (17/304, 5.6%). The positivity rate of these bacterial pathogens did not change significantly during the study period. Conclusions: NoV GII is the main pathogen in childhood AGE since the introduction of RV vaccine, yet the number of rotavirus-infected patients increased during our study, especially in 2018. Therefore, further research is needed including the possibility of emergence of novel RV strains. Campylobacter spp. is the predominant cause of bacterial AGE in children. For proper treatment, the clinical characteristics of the bacteria should be taken into consideration, and continuous monitoring is necessary.
Pneumonia is an infection of the lungs and respiratory system and can be classified by a variety of factors such as infectious agents, etiology, infection area, and other criteria. From a 46-year-old male, who was suspected of being infected with atypical pathogen pneumonia and underwent such tests as serological testing, examination of sputum, urine examination, parasite examination, bronchoscopy, needle biopsy and so on, no significant abnormality was found. This patient also showed no specific symptoms like auscultatory abnormalities, high fever, nonproductive cough, muscle stiffness, sputum production, dyspnea. Prescription of broad-spectrum oral antibiotics and ant-parasitic didn't seem to be effective against bacterial and atypical pathogen. The patient's condition alternately repeated between natural cure and recurrence. The average healing process during which scarring, nodule recurrence and disappearance on the lungs happened was about 20 days. Chest radiography and chest high resolution computerized tomographic scans(HRCT scan) was performed to depict parenchymal aberrations and demarcate the extent and distribution of atypical pathogen pneumonia. As a result, chest radiography did not show the specific symptoms, whereas areas of opacity (seen as white) which represent consolidation were revealed in chest HRCT scan. This indicates that only chest radiography is not that useful for early diagnosis of atypical pathogen pneumonia in patients, since it can't show exactly what the symptom is because of the barriers such as diaphragm, liver, and spine. Therefore, it is desirable that chest HRCT should be used in the diagnosis to compare with the results of chest radiography. Here, report with literature investigations the case of recurrent atypical pathogen pneumonia.
Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp.-CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary.
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