• 제목/요약/키워드: cause of disease and pathogenesis

검색결과 171건 처리시간 0.03초

Cytokine Storm Related to CD4+ T Cells in Influenza Virus-Associated Acute Necrotizing Encephalopathy

  • Shushu Wang;Dongyao Wang;Xuesong Wang;Mingwu Chen;Yanshi Wang;Haoquan Zhou;Yonggang Zhou;Yong Lv;Haiming Wei
    • IMMUNE NETWORK
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    • 제24권2호
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    • pp.18.1-18.12
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    • 2024
  • Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients' CD4+ T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+ T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

이상지질혈증과 치료제 연구개발 경향 (Drug research and development tend to hyperlipidemia)

  • 설인찬
    • 혜화의학회지
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    • 제18권2호
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    • pp.1-12
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    • 2009
  • Most of the cholesterol is synthesized by liver in the body while about one of third is taken via dietary. The main functions of cholesterol is to protect membranes in cell surface, avoid the arterial bleeding by hypertension, and prolong the life of erythrocytes, and so on. However, overload of cholesterol leads to arteriosclerosis associated with leading death cause. Lack of physical activity, emotional and environmental stress, and low intake of protein or vitamin E induce the unbalance between HDL- and LDL-cholesterol so become a basis of ischemic disorders in heart, brain and elsewhere in the body. So far, four major classes of medications for hyperlipidemia are HMG-CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid, and fibric acids. The statins can lower LDL and levels triglyceride, but may induce myopathy and an elevation of liver enzyme levels. The bile acid sequestrants lower LDL levels and raise HDL levels with no effect on triglyceride levels but side effects of gastrointestinal (GI) distress, constipation, and a decrease in the absorption of other drugs. Nicotinic acid and fibric acids lower LDL and triglyceride levels with showing flushing, hyperglycemia, hyperuricemia, GI distress, and hepatotoxicity dyspepsia, gallstones, myopathy, and unexplained noncardiac death as adverse effects. Above western drugs lower cholesterol by 15 to 30% while all have notable adverse effects. In traditional medicine, hyperlipidemia is regarded as retention of phlegm and fluid disease. Etiology and pathogenesis of hyperlipidemia is basically based on Spleen-Deficiency and Phlegm-Stagnation, accumulation and stasis of -heat, and Qi & blood stagnation induced by Phlegm-damp, water-dampness, and blood stasis. Thereby, strengthening Spleen and dissolving Phlegm, clearing away heat and diuresis, and supplementing Qi and activating blood circulation are commonly used therapeutic methods for hyperlipidemia. The traditional herbal medicine, have been used for patients with CVA, hypertension or hyperlipidemia in Oriental hospital or Oriental clinic. The lock and key theory is used to develop most of western medicine, however many diseases are caused by mixed factors in body-complex system. We expect that Oriental pharmacological theory could be newborn as a novel drug showing high advantage of blood levels of lipidsand QOL of performance without side effects.

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Sonicated Protein Fractions of Mycoplasma hyopneumoniae Induce Inflammatory Responses and Differential Gene Expression in a Murine Alveolar Macrophage Cell Line

  • Damte, Dereje;Lee, Seung-Jin;Birhanu, Biruk Tesfaye;Suh, Joo-Won;Park, Seung-Chun
    • Journal of Microbiology and Biotechnology
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    • 제25권12호
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    • pp.2153-2159
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    • 2015
  • Mycoplasma hyopneumoniae is known to cause porcine enzootic pneumonia (EP), an important disease in swine production. The objective of this study was to examine the effects of sonicated protein fractions of M. hyopneumoniae on inflammatory response and gene expression in the murine alveolar macrophage MH-S cell line. The effects of sonicated protein fractions and intact M. hyopneumoniae on the gene expression of cytokines and iNOS were assessed using RT-PCR. The Annealing Control Primer (ACP)-based PCR method was used to screen differentially expressed genes. Increased transcription of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, COX-2, and iNOS mRNA was observed after exposure to the supernatant (SPT), precipitant (PPT), and intact M. hyopneumoniae protein. A time-dependent analysis of the mRNA expression revealed an upregulation after 4 h for IL-6 and iNOS and after 12 h for IL-1β and TNF-α, for both SPT and PPT; the fold change in COX-2 expression was less. A dose- and time-dependent correlation was observed in nitrite (NO) production for both protein fractions; however, there was no significant difference between the effects of the two protein fractions. In a differential gene analysis, PCR revealed differential expression for nine gene bands after 3 h of stimulation — only one gene was downregulated, while the remaining eight were upregulated. The results of this study provide insights that help improve our understanding of the mechanisms underlying the pathogenesis of and macrophage defenses against M. hyopneumoniae assault, and suggest targets for future studies on therapeutic interventions for M. hyopneumoniae infections.

Comparison of Protein Electrophoresis Fractions in the Leptospirosis Patient Serum

  • Kim Chong Ho;Park Seung-Taeck;Oh Geum-Ga
    • 대한의생명과학회지
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    • 제10권3호
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    • pp.253-257
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    • 2004
  • The mechanisms by which leptospires caused disease are not well understood. A number of putative virulence factors have been suggested, but with few exceptions their role in pathogenesis remains unclear. In these days, many cases of leptospirosis are diagnosed by serological immunoassay. Leptospirosis is characterized by the histopathology of liver, kidney, heart, and lung, but the electrophoresis fractions of serum protein are not compared. We analyzed total protein, albumin, aspartic aminotranferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine and urea nitrogen (UN) in sera of patients diagnosed leptospirosis. Total protein and albumin were decreased in 18.5% and 31.2% of patients, respectively. AST, ALT, ALP, UN and creatinine were increased in 90.4%, 66.9%, 28.0%, 15.9% and 10.8% of patients, respectively. We performed cellulose acetate membrane electrophoresis (EP) on sera of patients increased both of AST and ALT, and of patients increased both of creatinine and UN. In patients increased both of AST and ALT, and in patients increased both of AST and ALT, the relative percentage of albumin to total protein in patient serum was dcreased in 89.1 % of patients. α₁-globulin, α₂-globulin, β-globulin and γ-globulin were increased in 85.1 %, 75.2%, 33.6% and 98.0% of patients, respectively. In patients increased both of creatinine and UN, the relative percentage of albumin to total protein in patient serum was dcreased in 93.8% of patients. α₁-globulin, α₂-globulin, β-globulin and γ-globulin were increased in 87.5%, 100%, 31.2% and 93.8% of patients, respectively. These data indicate that infection of Leptospira causes severe liver damage to most of leptospirosis patients, but doesn't cause renal damage to most of them. The relative rate of serum protein electrophoresis fractions to total protein are not identical with them of typical hepatitis patient.

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Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines

  • Xing Wei;Chin Wen Png;Madhushanee Weerasooriya;Heng Li;Chenchen Zhu;Guiping Chen;Chuan Xu;Yongliang Zhang;Xiaohong Xu
    • IMMUNE NETWORK
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    • 제23권4호
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    • pp.34.1-34.15
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    • 2023
  • Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

Molecular Mechanism of Runx2-Dependent Bone Development

  • Komori, Toshihisa
    • Molecules and Cells
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    • 제43권2호
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    • pp.168-175
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    • 2020
  • Runx2 is an essential transcription factor for skeletal development. It is expressed in multipotent mesenchymal cells, osteoblast-lineage cells, and chondrocytes. Runx2 plays a major role in chondrocyte maturation, and Runx3 is partly involved. Runx2 regulates chondrocyte proliferation by directly regulating Ihh expression. It also determines whether chondrocytes become those that form transient cartilage or permanent cartilage, and functions in the pathogenesis of osteoarthritis. Runx2 is essential for osteoblast differentiation and is required for the proliferation of osteoprogenitors. Ihh is required for Runx2 expression in osteoprogenitors, and hedgehog signaling and Runx2 induce the differentiation of osteoprogenitors to preosteoblasts in endochondral bone. Runx2 induces Sp7 expression, and Runx2, Sp7, and canonical Wnt signaling are required for the differentiation of preosteoblasts to immature osteoblasts. It also induces the proliferation of osteoprogenitors by directly regulating the expression of Fgfr2 and Fgfr3. Furthermore, Runx2 induces the proliferation of mesenchymal cells and their commitment into osteoblast-lineage cells through the induction of hedgehog (Gli1, Ptch1, Ihh), Fgf (Fgfr2, Fgfr3), Wnt (Tcf7, Wnt10b), and Pthlh (Pth1r) signaling pathway gene expression in calvaria, and more than a half-dosage of Runx2 is required for their expression. This is a major cause of cleidocranial dysplasia, which is caused by heterozygous mutation of RUNX2. Cbfb, which is a co-transcription factor that forms a heterodimer with Runx2, enhances DNA binding of Runx2 and stabilizes Runx2 protein by inhibiting its ubiquitination. Thus, Runx2/Cbfb regulates the proliferation and differentiation of chondrocytes and osteoblast-lineage cells by activating multiple signaling pathways and via their reciprocal regulation.

Cold Exposure and Health Effects Among Frozen Food Processing Workers in Eastern Thailand

  • Thetkathuek, Anamai;Yingratanasuk, Tanongsak;Jaidee, Wanlop;Ekburanawat, Wiwat
    • Safety and Health at Work
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    • 제6권1호
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    • pp.56-61
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    • 2015
  • Frozen food processing workers work under a cold environment which can cause several adverse health effects.This study explored factors affecting workers' health in the frozen food industry in Thailand. Participants comprised 497 workers exposed to a cold working environment and 255 office workers who served as the controls. Data were collected by a survey on the work environment, and the interview of workers for abnormal symptoms. The exposed group had the following characteristics: 52.7% male, overall average age of 27 (SD 6.6) years old, attained elementary education (Grade 4 and Grade 6) (54.1%), married (48.9%), smokers (21.3%), alcohol consumption (31.0%), duration of work was between 1 and 5 years (65.2%), working 6 days a week (82.7%), 1-5 hours of overtime per week (33.8%), office workers (33.9%); work category: sizing (6.9%), peeling (28.3%) dissecting (22.2%), and in the warehouse (8.6%). The temperature in the work environment ranged from $17.2^{\circ}C$ to $19.2^{\circ}C$ in most sections, $-18.0^{\circ}C$ in the warehouse, and $25^{\circ}C$ in the office areas. Warehouse workers had more abnormal symptoms than controls including repeated pain in the musculoskeletal system (OR 11.9; 95% CI 6.12-23.45), disturbance throughout the body (OR 4.60; 95% CI 2.00-10.56), respiratory symptoms (OR 9.73; 95% CI 3.53-26.80), episodic finger symptoms (OR 13.51; 95% CI 5.17-35.33). The study results suggest that workers' health should be monitored especially with regard to back and muscle pain, respiratory symptoms, episodic finger symptoms, and cardiovascular symptoms. Health promotion campaigns such as antismoking and reduction of alcohol consumption should be established because smoking and alcohol consumption are contributing factors to the pathogenesis of Raynaud's phenomenon and peripheral vascular disorders such as hypertension and heart disease.

설 기저부에 발생한 염증성 가성종양 1예 (A Case of Inflammatory Pseudotumor at Tongue Base)

  • 이현섭;허세형;진성민;이상혁
    • 대한후두음성언어의학회지
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    • 제22권1호
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    • pp.56-59
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    • 2011
  • Inflammatory pseudotumor is characterized by the presence of a mass that may mimic malignancy and is composed of spindle cells mixed with variable amounts of extracellular collagen, lymphocytes, and plasma cells It is benign tumor commonly involves lung and orbit and rarely that occurs in the head and neck The cause and pathogenesis of inflammatory pseudotumor still remain controversial. Some bacterial infection or chronic irritation may have prompted some speculation that an initially reactive process can change into an overt neoplastic disease. It tends to affect children and young adults than old ages. We present a case of inflammatory pseudotumor involving the tongue base, in a 73-year-old patient with repeated oral bleeding that aggravated over a few days. Clinical examination showed angiomatous polyp like findings in oropharynx that easy bleeding tendency. CT images showed well defined soft tissue mass with focal enhancement. After surgery, tumor was finally diagnosed inflammatory pseudotumor by histopathologic examinations showed plasma cells and inflammatory cells in variable fibrotic tissues.

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A Histone Deacetylase, MoHDA1 Regulates Asexual Development and Virulence in the Rice Blast Fungus

  • Kim, Taehyun;Lee, Song Hee;Oh, Young Taek;Jeon, Junhyun
    • The Plant Pathology Journal
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    • 제36권4호
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    • pp.314-322
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    • 2020
  • Interplay between histone acetylation and deacetylation is one of the key components in epigenetic regulation of transcription. Here we report the requirement of MoHDA1-mediated histone deacetylation during asexual development and pathogenesis for the rice blast fungus, Magnaporthe oryzae. Structural similarity and phylogenetic analysis suggested that MoHDA1 is an ortholog of Saccharomyces cerevisiae Hda1, which is a representative member of class II histone deacetylases. Targeted deletion of MoHDA1 caused a little decrease in radial growth and large reduction in asexual sporulation. Comparison of acetylation levels for H3K9 and H3K14 showed that lack of MoHDA1 gene led to significant increase in H3K9 and H3K14 acetylation level, compared to the wild-type and complementation strain, confirming that it is a bona fide histone deacetylase. Expression analysis on some of the key genes involved in asexual reproduction under sporulation-promoting condition showed almost no differences among strains, except for MoCON6 gene, which was up-regulated more than 6-fold in the mutant than wild-type. Although the deletion mutant displayed little defects in germination and subsequent appressorium formation, the mutant was compromised in its ability to cause disease. Wound-inoculation showed that the mutant is impaired in invasive growth as well. We found that the mutant was defective in appressorium-mediated penetration of host, but did not lose the ability to grow on the media containing H2O2. Taken together, our data suggest that MoHDA1-dependent histone deacetylation is important for efficient asexual development and infection of host plants in M. oryzae.

Lack of association between the VEGFA gene polymorphisms and preterm birth in Korean women

  • Yue Shi;Hyung Jun Kim;Seong Yong Kim;Ga Eun Kim;Han Jun Jin
    • Genomics & Informatics
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    • 제21권3호
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    • pp.29.1-29.9
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    • 2023
  • Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.