• Journal of Biomedical Engineering Research
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• v.40 no.1
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• pp.1-6
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• 2019

Human mesenchymal stem cells (hMSC) are multipotent stromal cells that have great potential to differentiate into a variety of cell types such as osteocytes, chondrocytes, and myocytes. Although there have been many studies on their clinical availability, little is known about how intracellular signals can be modulated by topographic features of the extracellular matrix (ECM). In this study, we investigated whether and how microwavy-patterned extracellular matrix (ECM) could affect the signaling activity of focal adhesion kinase (FAK), a key cellular adhesion protein. The fluorescence resonance energy transfer (FRET)-based FAK biosensor-transfected cells are incubated on microwavy-patterned surfaces and then platelet derived growth factor (PDGF) are treated to trigger FAK signals, followed by monitoring through live-cell FRET imaging in real time. As a result, we report that PDGF-induced FAK was highly activated in cells cultured on microwavy-patterned surface with L or M type, while inhibited by H type-patterned surface. In further studies, PDGF-induced FAK signals are regulated by functional support of actin filaments, microtubules, myosin-related proteins, suggesting that PDGF-induced FAK signals in hMSC upon microwavy surfaces are dependent on cytoskeleton (CSK)-actomyosin networks. Thus, our findings not only provide new insight on molecular mechanisms on how FAK signals can be regulated by distinct topographical cues of the ECM, but also may offer advantages in potential applications for regenerative medicine and tissue engineering.

• BMB Reports
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• v.52 no.6
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• pp.379-384
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• 2019

Epithelial-mesenchymal transition (EMT) is widely-considered to be a modulating factor of anoikis and cancer metastasis. We found that, in MDA-MB-231 cells, TP53I11 (tumor protein P53 inducible protein 11) suppressed EMT and migration in vitro, and inhibited metastasis in vivo. Our findings showed that hypoxic treatment upregulated the expression of $HIF1{\alpha}$, but reduced TP53I11 protein levels and TP53I11 overexpression reduced $HIF1{\alpha}$ expression under normal culture and hypoxicconditions, and in xenografts of MDA-MB-231 cells. Considering $HIF1{\alpha}$ is a master regulator of the hypoxic response and that hypoxia is a crucial trigger of cancer metastasis, our study suggests that TP53I11 may suppress EMT and metastasis by reducing $HIF1{\alpha}$ protein levels in breast cancer cells.

• 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.

• 한국사회정책
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• v.20 no.3
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• pp.197-221
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• 2013

The 2008 world economic crisis had unprecedented consequences in European societies, with repercussions on Southern European countries in particular. In Italy, the crisis itself provided a plausible rationale for policy makers to push forward long needed welfare cuts, resulting in the neoliberal austerity trend fostered by the Monti government (years 2011-2012). In the light of the fact that Bismarckian welfare states from continental Europe are generally difficult to reform, understanding these policy dynamics requires an adequate theoretical framework. This paper seeks to understand the logics behind welfare reforms in Italy after the 2008 economic crisis, by reviewing available theoretical approaches in literature. It is argued that external forces (notably, the European Union) represented the main trigger factor, and that political elites marginalized the role played by civil society, with social problems such as unemployment worsening as a result.

• Journal of Microbiology and Biotechnology
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• v.32 no.5
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• pp.645-656
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• 2022

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.111-117
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• 2013

Objectives : This research aimed at studying the immuno modulating activity of Fermented Epimedii Herba (EHS). Method : The impacts on the cell viability, hydrogen peroxide and nitric oxide (NO) generation in cells, and cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin (IL)-6, IL-$1{\beta}$, monocyte chemoattractant protein-1 (MCP-1) level have been measured by using Raw 264.7 cells with the specimen EHS as the fermented extract of Epimedii Herba with Saccharomyces cerevisiae STV89. Result : As a result of MTT assay to confirm the cytotoxicity of extracts from fermented Epimedii Herba, the toxicity was not excessively induced in Raw 264.7 cells when EHS were processed by concentration. EHS increased hydrogen peroxide generation in Raw 264.7 cells. EHS suppressed NO generation in Raw 264.7 cells while they significantly suppressed the increase of NO generation induced by LPS in macrophage. EHS significantly decreased the generation amount of TNF-${\alpha}$ and IL-6 induced by LPS in Raw 264.7 cells at $25{\mu}g/mL$ or more. Conclusion : It appeared that the fermented extract of Epimedii Herba manufactured from Epimedii Herba significantly has the immuno modulating acitivity as it did not excessively trigger cytotoxicity to Raw 264.7 cells, increased hydrogen peroxide generation in Raw 264.7 cells, decreased NO generation in macrophage, and especially, suppressed both TNF-${\alpha}$ and IL-6 generation in macrophage induced by LPS.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.3
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• pp.194-210
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• 2022

Human milk contains a number of nutritional and bioactive molecules including microorganisms that constitute the so-called "Human Milk Microbiota (HMM)". Recent studies have shown that not only bacterial but also viral, fungal, and archaeal components are present in the HMM. Previous research has established, a "core" microbiome, consisting of Firmicutes (i.e., Streptococcus, Staphylococcus), Proteobacteria (i.e., Serratia, Pseudomonas, Ralstonia, Sphingomonas, Bradyrhizobium), and Actinobacteria (i.e., Propionibacterium, Corynebacterium). This review aims to summarize the main characteristics of HMM and the role it plays in shaping a child's health. We reviewed the most recent literature on the topic (2019-2021), using the PubMed database. The main sources of HMM origin were identified as the retrograde flow and the entero-mammary pathway. Several factors can influence its composition, such as maternal body mass index and diet, use of antibiotics, time and type of delivery, and mode of breastfeeding. The COVID-19 pandemic, by altering the mother-infant dyad and modifying many of our previous habits, has emerged as a new risk factor for the modification of HMM. HMM is an important contributor to gastrointestinal colonization in children and therefore, it is fundamental to avoid any form of perturbation in the HMM that can alter the microbial equilibrium, especially in the first 100 days of life. Microbial dysbiosis can be a trigger point for the development of necrotizing enterocolitis, especially in preterm infants, and for onset of chronic diseases, such as asthma and obesity, later in life.

• International Journal of Computer Science & Network Security
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• v.24 no.3
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• pp.135-141
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• 2024

The article examines the key constants of reengineering the modern educational cluster, associated with the processes of digital transformation of all spheres of modern socio-cultural space. The first constant is the strategic rethinking of the educational process organization and awareness of the new roles of all participants (tutors, applicants, controlling elements, etc.). The other constant involves practical re-design of the system of educational services, which consists in the reorientation from the traditional model of education functioning for society to the implementation of the educational format in the form of new projects (structural, target, business). Consequently, the purpose of the study is to highlight the attitudes relevant to the modern realities of information and technological support of education in the context of socio-economic interactions of society. The criteria for the reengineering of educational concepts and the structural organization of the educational sphere are defined. The modern world is going through a period of complete digital transformation of all spheres of public activity. The scientific intelligence notes that education is no exception in these processes, as the dependence of educational realities on information and computer technologies is now noted. The COVID-19 pandemic, for all its tragedy, was also a kind of trigger, clearly marking the new components that have become defined in the organization of the educational process. The conclusion is made that the use of digital technologies in the organization of the educational institution or in the organization of the educational process has become not an auxiliary element, but a dominant factor. Mobility, dynamism, interdisciplinarity, synergy - all these aspects are relevant for socio-economic interactions of society and should be provided by educational programs. The results of the study can be used in the reorganization processes of educational institutions and institutions. Further research requires aspects of the analysis of the foreign experience of reengineering in education, carried out taking into account digital transformations of modern sociocultural space.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.304-312
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• 2023

Purpose: Due to the many problems with commercially available vaccines, the production of effective vaccines against brucellosis is a necessity. The aim of this study was to evaluate the immune responses caused by the chimeric protein consisting of trigger factor, Bp26, and Omp31 (TBO) along with aluminum hydroxide (AH/TBO) and selenium (Se/TBO) nanoparticles (NPs) as adjuvants in mouse model. Materials and Methods: Recombinant antigen expression was induced in Escherichia coli BL21 (DE3) bacteria using IPTG (isopropyl-d-1-thiogalactopyranoside). Purification and characterization of recombinant protein was conducted through NiFe₃O₄ NPs, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blot. NP characteristics, including morphology and particle size, were measured in vitro. The recombinant TBO was loaded on to AH and Se NPs and were administered subcutaneously. After mice immunization, measurement of antibody titter and protection assay was performed. Results: The average sizes of AH and Se NPs were about 60 nm and 150 nm, respectively. The enzyme-linked immunosorbent assay results showed that the serum of mice immunized by subcutaneous injection with both nanovaccines produced significant immunoglobulin G (IgG) responses against the chimeric antigen. The results of TBO-specific IgG isotype (IgG2a/IgG1) analysis showed that both AH and Se NPs induced a type to T-helper immune response. In addition, the results of the challenge with the pathogenic strain of Brucella melitensis 16M showed that vaccinated mice with AH/TBO NPs indicated a higher reduction of bacterial culture than immunized mice with Se/TBO NPs and TBO alone. Conclusion: The results showed that AH NPs carrying chimeric antigen can be a promising vaccine candidate against brucellosis by producing protective immunity.

• Journal of Veterinary Clinics
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• v.28 no.2
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• pp.196-203
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• 2011

Staphylococcus spp. is one of the most common bacteria isolated from the lesions of atopic dermatitis (AD) in humans, and their colonization is known to be a possible trigger factor of clinical signs. The aim of this study was to determine the prevalence of Staphylococcus spp. in canine AD (CAD), the types of exotoxins present, and their relation with the clinical severity of CAD. From 79 dogs with AD, 72 samples of Staphylococcus spp. were isolated (91.1%), and 65 (90.3%) were confirmed as Staphylococcus pseudintermedius. Concerning the profile of the exotoxin gene, 50 isolates (69.4%) contained at least one exotoxin gene, and 28 isolates (56%) were found to contain more than 2 different exotoxins. There was a significant difference in clinical severity with the presence of staphylococcal exotoxins (P=0.028), whereas no correlation was found with the presence of Staphylococcus spp. (P=0.598). The clinical severity of CAD increased only in relation to staphylococcal enterotoxin D (SED) and exfoliative toxins (P<0.05). Some clinical evaluation criteria (erythema, papule/pustule) were correlated with the presence of the exotoxin gene (P<0.05). This study showed that the high prevalence of Staphylococcus spp. and staphylococcal exotoxins in lesions from dogs with AD may be regarded as an important trigger factor for exacerbation of the clinical signs of CAD.