• Archives of Pharmacal Research
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• v.20 no.2
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• pp.128-137
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• 1997

The effects of cylindan, a polysaccharide isolated from the basidiocarps of Agrocybe cylindracea, on murine sarcoma 180 tumor and murine immune cells were examined after intraperitoneal administration. Cylindan exhibited a marked life extension effect in mice against ascite forms of sarcoma 180 and Lewis lung carcinoma at a dose of 50 mg/kg/day, although it did not show any direct cytotoxicity against sarcoma 180, X5563, and MM46 murine tumor cells. Cylindan increased numbers of bone marrow stem cells as well as peritoneal exudate cells in flow cytometry using monoclonal antibodies. The tumor bearing mice group apparently showed the increase of macrophages and cytotoxic T lymphocytes in mouse spleen cells during the early stage of tumor growth. But during the later stage, the control group decreased immune cells and cylindan restored the decreased immune cells in the tumor bearing mice to the normal level. In non-specific immune response, cylindan stimulated the bacterial phagocytosis and acid phosphatase production in macrophages. It also activated components of the alternative complement pathway and natural killer activity against YAC-1 lymphoma. In number of plasma cells as token of stimulation of the differentiation of B lymphocytes. In cellular immunity, cylindan restored the depressed response of delayed type hypersensitivity in the tumor bearing mice to 60% of the normal level and increased the interleukin-2 (IL-2) responsiveness in the IL-2 dependent CTLL-2 cells. These results suggest that cylindan did not show direct cytotoxic effects on tumor cells but restored the decreased immune response of the tumor bearing mice.

• The Korean Journal of Physiology
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• v.29 no.1
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• pp.1-11
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• 1995

Alveolar macrophages play a pivotal role in the pathogenesis of silicosis since the macrophages may release a wide variety of toxic and inflammatory mediators as well as mitogenic growth factors. In the present study, the effects of in vitro exposure to silica on release of various mediator such as reactive oxygen species, platelet activating factor(PAF), and interleukin-1 (IL-1) by alveolar macrophages were examined. First, hydrogen peroxide release from alveolar macrophages was monitored by measuring the change in fluorescence of scopoletin in the absence or presence of graded concentration of silica. Significantly enhanced release of hydrogen peroxide was observed at 0.5 mg/ml and above. A maximal enhancement of 10 fold above control was observed at 5 mg/ml silica. Similarly, in vitro exposure to silica also significantly stimulated the generation of chemiluminescence from alveolar macrophages at 0.5 mg/ml and above with n maximal enhancement of 8 fold at 5 mg/ml silica. Second, PAF release from alveolar macrophages after 30 min incubation at $37^{\circ}C$ in absence or presence of zymosan and silica was determined by measuring $^{3}H-serotonin$ release ability of the conditioned macrophage supernates from platelets. 5 mg/ml zymosan as a positive control fur the PAF assay increased PAF release by 19 % of total serotonin release. Furthermore, silica also resulted in significant enhancement of the PAF release compared with that in unstimulated (control) cells, i.e., $17.7{\pm}5.8%$ and $24.0{\pm}4.9%$ of total serotonin release at 5 mg/ml and 10 mg/ml silica, respectively, which represents the release of nanomole levels of PAF. Lastly, IL-1 production by alveolar macrophages was analysed following their stimulation with lipopolysaccharide (LPS) and silica by their capacity to stimulate thymocyte proliferation. $10\;{\mu}g/ml$ LPS resulted in an 11 fold increase in IL-1 production. In comparison, $50\;{\mu}g/ml$ silica resulted in a 4 fold increase in IL-1 release. These data indicate that in vitro exposure of alveolar macrophages to silica activates the release of various bioactive mediators such as reactive oxygen species, PAF and IL-1 which thus contribute to amplification of inflammatory reactions and regulation of fibrotic responses by the lung after inhalation of silica.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2953-2957
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• 2016

Background: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked ${\beta}2-adrenergic$ receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. Materials and Methods: We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel-Haenszel, Student t, and ANOVA tests were performed for data analysis. Results: On average, patients were $54.8{\pm}11.8$ years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for ${\beta}1$ - and ${\beta}2$ -adrenergic-receptors did not present metastasis globally, but patients treated with ${\beta}1$ BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. Conclusions: In Mexican patients with BCa and SAH treated with non-selective (${\beta}1$- and ${\beta}2-adrenergic$ receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.610-616
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• 2021

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood. Methods: We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis. Results: Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3. Conclusion: Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

• International Journal of Computer Science & Network Security
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• v.21 no.7
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• pp.125-132
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• 2021

Rapid growth of the higher education role in ensuring the socio-economic and innovative development of the national economy in the context of the development of the information society and the knowledge economy is observed. Achieving positive synergistic effects of the higher education development requires proper funding for university education and research. The existing funding models for national higher education systems in a number of developing countries need modernization in accordance with the modern challenges of economic and innovative development. The purpose of the article is to formulate theoretical - methodological and applied foundations for the development and implementation of the integrated model of the higher education financing under the Quadruple Helix concept. At the center of the developed model are the areas of interaction identified by the authors, namely: Personnel, Science, Management, Innovation, Social area. This made it possible to specify the interests of all stakeholders and orient the activities of higher education institutions to the satisfaction of these interests. Effective implementation of the integrated Model of the higher education financing requires increasing the level of investment attractiveness and practical value of university research; activation of innovative development of enterprises; state stimulation of business participation in university research and education; harmonization of current legislation with EU standards. Implementation of the Model will diversify sources of funding for universities, increase their level of economic security and achieve integrated synergies from the interaction of universities, business, government and the public (as the main stakeholders within the Quadruple Helix concept).

• Biomedical Science Letters
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• v.24 no.4
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• pp.372-379
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• 2018

Korean society is experiencing rapid growth due to industrialization and urbanization, and the aging of population is emerging. Degradation of the masticatory muscle due to aging and reduction of the number of mastications causes dry mouth syndrome with decreased saliva in the elderly. Changes in the amount and composition of saliva cause various oral diseases, especially, periodontal disease is closely related to the microorganisms that form the plaque. In the elderly education, stimulation saliva was collected at the first visit and the last visit to observe changes in microorganisms in the oral cavity. For the collection of the probes, the paraffin wax was chewed for 5 minutes. The samples were immediately refrigerated in a 50 cc plastic tube and then stored at $-20^{\circ}C$ until the next use. The subjects of this study were the elderly people aged 65 years or older, and the study was conducted on 16 persons, 3 males and 13 females. The distribution of saliva microorganisms according to rolling brushing method showed significant difference in all three groups (Aa & Red complex, Orange complex and Green complex) before and after the education. In the group who answered that they had dentures, it was confirmed that the amount of microorganisms before and after education was significantly reduced in all three groups. There was a significant decrease in the amount of microorganisms in the Aa & Red complex and Orange complex group in the case of hypertension related to systemic disease. In conclusion, the higher the interest of oral health and general health of the subjects, the more effective the education.

• Parasites, Hosts and Diseases
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• v.57 no.2
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• pp.117-125
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• 2019

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of $HIF1{\alpha}$ through an intracellular oxygen-sensing pathway. Activation of $HIF1{\alpha}$ may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of $2{\times}10^6$ parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and $HIF1{\alpha}$. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and $HIF1{\alpha}$ increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxiainduced angiogenesis by stimulation of $HIF1{\alpha}$ and VEGF in various tissues.

• Food Engineering Progress
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• v.21 no.2
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• pp.126-131
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• 2017

Millimeter waves are electromagnetic waves with frequencies of 30-300 GHz (wavelength 1-10 mm), and millimeter wave stimulation affects microorganism growth. The present study stimulated Bacillus subtilis with 60 and 70 GHz millimeter waves during cheonggukjang fermentation and characterized the effects on cheonggukjang quality. Cheonggukjang treated with millimeter wave irradiation showed no significant difference in total bacterial count but generated only 5.52-5.92% viscous substance. Irradiation with 60 GHz millimeter waves yielded bright and intense color values relative to 70 GHz millimeter waves. Examination of the amylase activity and reducing sugar content of finished cheonggukjang revealed that irradiation at 70 GHz inhibited amylase activity in cheonggukjang. Furthermore, irradiation at 70 GHz increased protease activity, whereas irradiation at 60 GHz inhibited the activity. Moreover, the amino acid content changed with millimeter wave irradiation.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.545-550
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• 2021

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

• Journal of dental hygiene science
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• v.21 no.4
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• pp.227-232
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• 2021

Background: Cancer-associated fibroblasts (CAFs) are abundant in tumor microenvironments and interact with cancer cells to promote tumor proliferation in oral squamous cell carcinoma (OSCC). Cathepsin D (CTSD) is a soluble lysosomal aspartic endopeptidase involved in tumor proliferation and angiogenesis. In this preliminary study, we observed CTSD expression in OSCC and CAFs, postulating that CTSD might act as a bridge between OSCC and CAFs. Methods: Human epidermal keratinocytes (HEKs), OSCC, and immortalized human normal oral fibroblasts (hTERT-hNOFs) were used in this study. Additionally, we used hTERT-hNOFs transfected with an empty vector, WT (wild-type)-YAP (Yes-associated protein), and YAPS127A (YAP serine 127 to alanine). YAP127A hTERT-hNOFs activated fibroblasts similar to CAFs. To identify CTSD expression between OSCC and CAFs, conditioned medium (CM) was collected from each cell. Protein expression of CTSD was identified by western blotting. Results: To identify the expression of CTSD in fibroblasts stimulated by OSCC, we treated fibroblasts with CM from HEK and OSCC. Results indicated that hTERT-hNOFs with OSCC CM showed a weakly increased expression of CTSD compared to stimulation by HEK CM. This indicates that CAFs, YAPS127 hTRET-hNOFs, overexpress CTSD protein. HEK cells showed no CTSD expression, regardless of treatment with fibroblast CM, whereas OSCC highly expressed CTSD proteins compared with the CTSD expression in HEK cells. We also found that CTSD expression was unaffected by changes in transforming growth factor-β levels. Conclusion: This study proposes that CTSD might have potential as an interacting executor between OSCC and CAFs. Further studies are needed to investigate the role of CTSD in tumor and stromal cells.