• Title/Summary/Keyword: Immune dysfunction

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Synthetic Cannabinoid-Induced Immunosuppression Augments Cerebellar Dysfunction in Tetanus-Toxin Treated Mice

  • Yun, Jaesuk;Gu, Sun Mi;Lee, Tac-hyung;Song, Yun Jeong;Seong, Seonhwa;Kim, Young-Hoon;Cha, Hye Jin;Han, Kyoung Moon;Shin, Jisoon;Oh, Hokyung;Jung, Kikyung;Ahn, Chiyoung;Park, Hye-Kyung;Kim, Hyung Soo
    • Biomolecules & Therapeutics
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    • v.25 no.3
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    • pp.266-271
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    • 2017
  • Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.

Comparison of Blood Gas, Biochemical Factors, and Hormone Concentrations, and Muscle Stress Response Factors of Chickens in General Farms and Animal Welfare Farms (일반농장과 동물복지농장 닭의 혈액 내 gas, 생화학인자, 호르몬 농도 및 근육 내 스트레스 반응인자 비교)

  • Kim, Hee-Eun;Park, Jin-Ryong;Lee, Jeong-Eun;Kang, Da-Rae;Jang, Ae-Ra;Choe, Ho-Sung;Shim, Kwan-Seob
    • Korean Journal of Organic Agriculture
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    • v.29 no.3
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    • pp.415-427
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    • 2021
  • It is generally recognized that high stocking density can increase the risk of immune dysfunction and reduction in productivity cause of elevated stress in broiler farm. The domestic livestock industry is implementing a certification system for animal welfare and livestock farms to reduce the problem of dense breeding. This study compared broiler from the general farm and animal welfare farm to confirm the effectiveness of animal welfare farms against stress. Gas concentrations in a farm of general and animal welfare farms were analyzed, blood (n=10) of the 28-day-old broiler was collected, the partial pressure of the gas in the blood was analyzed using whole blood, and biochemical factors and hormones were analyzed using the serum. Glycogen and L-lactate are analyzed using ELISA kit on finely pulverized muscles (n=10). CO2 and NH3 levels in the farm were significantly higher in general farm. Partial carbon dioxide tension (PCO2) in blood was significantly higher and partial oxygen tension (PO2) was significantly lower in the general farm. Creatinine (CREA), glucose (GLU), aspartateaminotransferase (AST), and creatinekinase (CK) in the blood were significantly higher in the general farm, and total protein (TP) and globulin (GLOB) were significantly higher in animal welfare farm. Blood corticosterone and norepinephrine were significantly higher in general farm and epinephrine was significantly higher in animal welfare farm. These results imply that animal welfare farm provides a stress-reduced breeding environment.

LymphanaxTM Enhances Lymphangiogenesis in an Artificial Human Skin Model, Skin-lymph-on-a-chip (스킨-림프-칩 상에서 LymphanaxTM 의 림프 형성 촉진능)

  • Phil June Park;Minseop Kim;Sieun Choi;Hyun Soo Kim;Seok Chung
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.50 no.2
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    • pp.119-129
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    • 2024
  • The cutaneous lymphatic system in humans plays a crucial role in draining interstitial fluid and activating the immune system. Environmental factors, such as ultraviolet light and natural aging, often affect structural changes of such lymphatic vessels, causing skin dysfunction. However, some limitations still exist because of no alternatives to animal testing. To better understand the skin lymphatic system, a biomimetic microfluidic platform, skin-lymph-on-a-chip, was fabricated to develop a novel in vitro skin lymphatic model of humans and to investigate the molecular and physiological changes involved in lymphangiogenesis, the formation of lymphatic vessels. Briefly, the platform involved co-culturing differentiated primary normal human epidermal keratinocytes (NHEKs) and dermal lymphatic endothelial cells (HDLECs) in vitro. Based on our system, LymphanaxTM, which is a condensed Panax ginseng root extract obtained through thermal conversion for 21 days, was applied to evaluate the lymphangiogenic effect, and the changes in molecular factors were analyzed using a deep-learning-based algorithm. LymphanaxTM promoted healthy lymphangiogenesis in skin-lymphon-a-chip and indirectly affected HDELCs as its components rarely penetrated differentiated NHEKs in the chip. Overall, this study provides a new perspective on LymphanaxTM and its effects using an innovative in vitro system.

The Ability of Anti-tumor Necrosis Factor Alpha(TNF-${\alpha}$) Antibodies Produced in Sheep Colostrums

  • Yun, Sung-Seob
    • 한국유가공학회:학술대회논문집
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    • 2007.09a
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    • pp.49-58
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    • 2007
  • Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

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Clinical Applications and Efficacy of Korean Ginseng (고려인삼의 주요 효능과 그 임상적 응용)

  • Nam, Ki-Yeul
    • Journal of Ginseng Research
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    • v.26 no.3
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    • pp.111-131
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    • 2002
  • Korean ginseng (Panax ginseng C.A. Meyer) received a great deal of attention from the Orient and West as a tonic agent, health food and/or alternative herbal therapeutic agent. However, controversy with respect to scientific evidence on pharmacological effects especially, evaluation of clinical efficacy and the methodological approach still remains to be solved. Author reviewed those articles published since 1980 when pharmacodynamic studies on ginseng have intensively started. Special concern was paid on metabolic disorders including diabetes mellitus, circulatory disorders, malignant tumor, sexual dysfunction, and physical and mental performance to give clear information to those who are interested in pharmacological study of ginseng and to promote its clinical use. With respect to chronic diseases such as diabetes mellitus, atherosclerosis, high blood pressure, malignant disorders, and sexual disorders, it seems that ginseng plays preventive and restorative role rather than therapeutics. Particularly, ginseng plays a significant role in ameliorating subjective symptoms and preventing quality of life from deteriorating by long term exposure of chemical therapeutic agents. Also it seems that the potency of ginseng is mild, therefore it could be more effective when used concomitantly with conventional therapy. Clinical studies on the tonic effect of ginseng on work performance demonstrated that physical and mental dysfunction induced by various stresses are improved by increasing adaptability of physical condition. However, the results obtained from clinical studies cannot be mentioned in the indication, which are variable upon the scientist who performed those studies. In this respect, standardized ginseng product and providing planning of the systematic clinical research in double-blind randomized controlled trials are needed to assess the real efficacy for proposing ginseng indication. Pharmacological mode of action of ginseng has not yet been fully elucidated. Pharmacodynamic and pharmacokinetic researches reveal that the role of ginseng not seem to be confined to a given single organ. It has been known that ginseng plays a beneficial role in such general organs as central nervous, endocrine, metabolic, immune systems, which means ginseng improves general physical and mental conditons. Such multivalent effect of ginseng can be attributed to the main active component of ginseng,ginsenosides or non-saponin compounds which are also recently suggested to be another active ingredients. As is generally the similar case with other herbal medicines, effects of ginseng cannot be attributed as a given single compound or group of components. Diversified ingredients play synergistic or antagonistic role each other and act in harmonized manner. A few cases of adverse effect in clinical uses are reported, however, it is not observed when standardized ginseng products are used and recommended dose was administered. Unfavorable interaction with other drugs has also been suggested, which the information on the products and administered dosage are not available. However, efficacy, safety, interaction or contraindication with other medicines has to be more intensively investigated in order to promote clinical application of ginseng. For example, daily recommended doses per day are not agreement as 1-2g in the West and 3-6 g in the Orient. Duration of administration also seems variable according to the purpose. Two to three months are generally recommended to feel the benefit but time- and dose-dependent effects of ginseng still need to be solved from now on. Furthermore, the effect of ginsenosides transformed by the intestinal microflora, and differential effect associated with ginsenosides content and its composition also should be clinically evaluated in the future. In conclusion, the more wide-spread use of ginseng as a herbal medicine or nutraceutical supplement warrants the more rigorous investigations to assess its effacy and safety. In addition, a careful quality control of ginseng preparations should be done to ensure an acceptable standardization of commercial products.

Clinical Characteristics, Prognostic Factors and Influence of Prophylaxis in Children with Pneumocystis jirovecii Pneumonia (소아 주폐포자충 폐렴의 임상양상, 위험인자 및 예방요법의 효과 연구)

  • Kim, Seohee;Yoo, Reenar;Sung, Hungseop;Lee, Jina
    • Pediatric Infection and Vaccine
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    • v.23 no.1
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    • pp.31-39
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    • 2016
  • Purpose: The aim of this study was to investigate the prognostic factors for Pneumocystis jirovecii pneumonia (PCP) and to evaluate the influence of PCP prophylaxis in pediatric patients. Methods: From January 2002 to April 2015, patients aged <18 years with a diagnosis of confirmed PCP at our institute were reviewed retrospectively. Clinical characteristics and outcomes were compared according to the groups with or without PCP prophylaxis. Risk factors associated with PCP-related death were analyzed by logistic regression analysis. Results: During study period, a total of 24 patients were diagnosed with PCP by immunofluorescence assay and/or PCR. The median age of the patients was 5 years (range, 3 months-18 years) and 23 (96%) had immunocompromised conditions including hematologic disorders with or without hematopoietic stem cell transplantation (n=15), solid organ transplantation (n=4), and primary immune deficiency (n=4). Most common presenting symptoms were tachypnea and cough (92%, each). At the time of diagnosis, 79% (19/24) and 25% (6/24) suffered from respiratory failure and multi-organ dysfunction syndrome (MODS), respectively. Mechanical ventilation was required in 8 (33%) patients and 5 (21%) patients died of PCP. Multivariate analysis showed that MODS at initial presentation was an indicator of poor prognosis (OR, 17.1 [95% CI 1.13-257.67]; P=0.04). Compared to the patients without PCP prophylaxis, the frequency of MODS at diagnosis, need for mechanical ventilation and length of hospital days were significantly less common in the children who received PCP prophylaxis. Conclusions: MODS at presentation was a significant predictor for poor outcome and PCP prophylaxis could alleviate the clinical courses of pediatric PCP. Prospective study will be mandatory to determine the risk factors for development and deterioration of PCP in children.

Leptin, adiponectin, interleukin-6 and tumor necrosis factor-α in obese adolescents (비만아에서의 leptin, adiponectin, interleukin-6, tumor necrosis factor-α에 대한 연구)

  • Gil, Joo Hyun;Lee, Jung Ah;Kim, Ji Young;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.51 no.6
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    • pp.597-603
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    • 2008
  • Purpose : Obesity is associated with insulin resistance. Insulin resistance and the presence of pro-inflammatory mediators are thought to cause a state of vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation. These chronic inflammatory responses, which are characterized by abnormal cytokine production, lead to activation of a pro-inflammatory signaling pathway. Leptin is an important mediator of inflammatory processes and immune-mediated diseases. The purpose of this study was to investigate the relationship between leptin and various cytokines associated with obesity in adolescents. Methods : Sixty-six obese adolescents (between 16-17 years of age, obesity index >130%) and 26 normal controls were included in this study. Obesity index and body mass index (BMI) were calculated. Serum lipid profile, AST and ALT were tested after 10 hours of fasting. Tumor necrosis factor alpha (TNF-${\alpha}$) and Interleukin-6 (IL-6) levels were measured by ELISA. Insulin, adiponectin, and leptin levels were estimated by radioimmunoassay. Results : Leptin was significantly higher in the obese adolescents compared to the control adolescents ($12.0{\pm}6.8ng/mL$ vs $6.3{\pm}1.0ng/mL$). TNF-${\alpha}$, IL-6, and insulin were significantly higher in the obese adolescents. Adiponectin was significantly lower in the obese group than the control group ($3.3{\pm}1.9{\mu}g/mL$ vs $5.0{\pm}1.4{\mu}g/mL$). Leptin had positive correlations with obesity index, BMI, and IL-6. Conclusion : In obese adolescents, leptin, TNF-${\alpha}$, IL-6, and insulin might be important mediators of obesity. Further clinical research is necessary to ascertain leptin as a predictor of cardiovascular diseases and to develop a guideline for clinical intervention.