• IMMUNE NETWORK
• /
• v.22 no.4
• /
• pp.33.1-33.17
• /
• 2022

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

• IMMUNE NETWORK
• /
• v.20 no.5
• /
• pp.38.1-38.12
• /
• 2020

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3⁺ induced Treg (iTreg) differentiation in ovalbumin-specific CD4⁺ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.2
• /
• pp.476-483
• /
• 2024

Fractionated lipids of Halocynthia aurantium (Pyuridae) have been demonstrated to possess anti-inflammatory properties. However, their modulatory properties have not been reported yet. Thus, the objective of this study was to determine immune enhancing effects of fractionated lipids from H. aurantium tunic on macrophage cells. The tunic of H. aurantium was used to isolate total lipids, which were then subsequently separated into neutral lipids, glycolipids, and phospholipids. RAW264.7 cells were stimulated with different concentrations (0.5, 1.0, 2.0, and 4.0%) of each fractionated lipid. Cytotoxicity, production of NO, expression levels of immune-associated genes, and signaling pathways were then determined. Neutral lipids and glycolipids significantly stimulated NO and PGE₂ production and expression levels of IL-1β, IL-6, TNF-α, and COX-2 in a dose-dependent manner, while phospholipids ineffectively induced NO production and mRNA expression. Furthermore, it was found that both neutral lipids and glycolipids increased NF-κB p-65, p38, ERK1/2, and JNK phosphorylation, suggesting that these lipids might enhance immunity by activating NF-κB and MAPK signaling pathways. In addition, H. aurantium lipids-induced TNF-α expression was decreased by blocking MAPK or NF-κB signaling pathways. Phagocytic activity of RAW 264.7 cells was also significantly enhanced by neutral lipids and glycolipids. These results suggest that neutral lipids and glycolipids from H. aurantium tunic have potential as immune-enhancing materials.

• Annals of Occupational and Environmental Medicine
• /
• v.34
• /
• pp.29.1-29.14
• /
• 2022

Background: Hotel housekeepers are one of the most important occupational group within tourism hotel sector; various health problems related to their job have been described, above all musculoskeletal disorders. The objective of this study is to understand the experiences and perceptions of hotel housekeepers and key informants from the Balearic Islands (Spain) regarding occupational health conditions and the strategies employed to mitigate them. Methods: A qualitative study was carried out. Six focus groups with hotel housekeepers and 10 semi-structured interviews with key informants were conducted. Next, we carried out a content analysis. Results: Hotel housekeepers reported musculoskeletal disorders, anxiety and stress as main occupational health problems; health professionals underscored the physical problems. Hotel housekeepers perceived that their work (physically demanding and with repetitive movements) caused their health conditions. To solve health issues, they used medication (anti-inflammatory agents, painkillers, sedatives and anxiolytics), which allowed them to continue working; health public services, generally rated as satisfactory; individual protective equipment; ergonomics (with difficulties due to high work pace and hotel facilities) and physical activity. Two contrasting attitudes were identified regarding sick leave: HHs who refused to accept a doctor-prescribed sick leave (due to fear of being fired, sense of responsibility, ...), and those who accepted it (because they could not continue working, they prioritised health before work). Conclusions: Our results might contribute to plan improvement strategies and programs to address health problems among hotel housekeepers. These programs should include interventions, such as coping strategies for the work-related risk factors (i.e., stress) and strategies to reduce medicine consumption. Additionally, hotel facilities should adopt policies focused on making workplaces more ergonomic (i.e., furniture) and to diminish the work pace.

• International Journal of Oncology
• /
• v.56 no.2
• /
• pp.630-640
• /
• 2020

Plant flavonoid 2',3,4',5,7-pentahydroxyflavone (morin hydrate), isolated from the family Moraceae (Morus alba L.), is known to have anti-inflammatory and anticancer effects. However, its pharmaceutical effects on metastasis have not been fully elucidated to date. Therefore, the current study investigated the effects of morin hydrate on cancer metastasis in MCF-7 human breast cancer cells. The results showed that morin hydrate suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion via the inhibition of matrix metalloproteinase (MMP)-9 activity. Furthermore, gene expression level of MMP-9, MMP-7, urokinase plasminogen activator (uPA), uPA receptor (uPAR) and fibronectin were significantly decreased by morin hydrate treatment. Morin hydrate inhibited the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β, and downregulated the expression of an activator protein-1 subunit c-Fos. In addition, the GSK-3β phosphorylation and c-Fos expression were suppressed by PI3K/Akt pathway inhibitors, LY294002 and wortmannin. Taken together, these results demonstrated that morin hydrate reduced the metastatic potential in TPA-treated MCF-7 human breast cancer cells via the inhibition of MMPs, uPA and uPAR, and the underlying Akt/GSK-3β/c-Fos pathway. Therefore, the present investigation suggested that morin hydrate may be a natural substance with a preventive potential for metastasis in breast cancer cells.

• Clinical and Experimental Reproductive Medicine
• /
• v.51 no.2
• /
• pp.112-119
• /
• 2024

Objective: Endometriosis is a common gynecological disease among reproductive-age women. Numerous hypotheses exist regarding the pathogenesis of endometriosis. In Turkey, the consumption of Allium cepa (commonly known as the "onion cure") is a popular treatment employed to alleviate a variety of gynecological disorders. Methods: In this study, our objective was to assess the therapeutic mechanisms of the onion bulb A. cepa using an autologous endometriosis model in Sprague-Dawley rats. Previous research has shown that A. cepa possesses anti-inflammatory, antioxidant, and antiapoptotic properties. We evaluated the pathological condition of endometriotic implants by employing hematoxylin-eosin staining and Ki67 immunohistochemistry analysis. Transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) have been identified as profibrotic markers that are highly overexpressed in endometriotic tissues relative to eutopic endometrial tissue. Furthermore, TGF-β1 influences the differentiation and progression of endometriosis. To quantify profibrotic activity, we measured TGF-β1 and α-SMA using the immunosorbent assay method. Results: Lower histologic evaluation scores for endometriotic implants were observed in the group receiving high-dose A. cepa relative to the other groups. Ki67 expression was reduced following the high-dose A. cepa regimen, which consisted of 30% A. cepa and 70% normal feed. However, no statistically significant differences in TGF-β1 or α-SMA levels were observed among the groups (p=0.7 and p=0.778, respectively). Conclusion: The findings suggest that A. cepa could serve as a therapeutic agent in endometriosis treatment, as evidenced by the reduction in proliferative potential. Nevertheless, A. cepa was not associated with significantly lower levels of endometriosis-associated TGF-β1 or α-SMA.

• Journal of Pharmacopuncture
• /
• v.27 no.3
• /
• pp.245-252
• /
• 2024

Objectives: Methotrexate (MTX), an immunosuppressant and anti-cancer medication, can harm the heart. The goal of the current investigation was to assess the cardiotoxicity caused by MTX and the potential cardioprotective properties of silymarin, citral, and thymoquinone as antioxidants. Methods: Forty-eight rats were divided into six groups, which included control, MTX, cosolvent, citral, thymoquinone, and silymarin groups. At the end of the study, the rats were anesthetized (ketamine and xylazine) and killed using CO2. Their blood samples were collected to measure the enzymatic activities of creatine kinase-myoglobin binding (CK-MB), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Also, the heart tissue was sampled to determine the antioxidant capacity and examine the histopathology. Results: The findings revealed that the activity of CPK, CK-MB, and LDH enzymes significantly reduced in the thymoquinone treatment group compared to the MTX group (p < 0.05). On the other hand, total antioxidant capacity was significantly increased in the thymoquinone group compared to the MTX group (p < 0.05). The pathological modifications (i.e. severe congestion, edema fluid, the presence of inflammatory cells around the blood vessels, mild to moderate hemorrhaging between cardiac muscle fibers) were seen in the MTX group. The treatment groups, particularly thymoquinone, did not experience any appreciable pathological changes. Conclusion: The thymoquinone was found to have the strongest protective effect against the heart damage caused by MTX.

• Journal of Life Science
• /
• v.30 no.11
• /
• pp.999-1006
• /
• 2020

The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH₂) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6633-6638
• /
• 2014

The Pharmacological potential, such as antioxidant, anti-inflammatory, and antibacterial activities of Portulaca oleracea (PO) and Petroselinum sativum (PS) extracts are well known. However, the preventive properties against hepatocellular carcinoma cells have not been explored so far. Therefore, the present investigation was designed to study the anticancer activity of seed extracts of PO and PS on the human hepatocellular carcinoma cells (HepG2). The HepG2 cells were exposed with $5-500{\mu}g/ml$ of PO and PS for 24 h. After the exposure, cell viability by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, neutral red uptake (NRU) assay, and cellular morphology by phase contrast inverted microscope were studied. The results showed that PO and PS extracts significantly reduced the cell viability of HepG2 in a concentration dependent manner. The cell viability was recorded to be 67%, 31%, 21%, and 17% at 50, 100, 250, and $500{\mu}g/ml$ of PO, respectively by MTT assay and 91%, 62%, 27%, and 18% at 50, 100, 250, and $500{\mu}g/ml$ of PO, respectively by NRU assay. PS exposed HepG2 cells with $100{\mu}g/ml$ and higher concentrations were also found to be cytotoxic. The decrease in the cell viability at 100, 250, and $500{\mu}g/ml$ of PS was recorded as 70%, 33%, and 15% by MTT assay and 63%, 29%, and 17%, respectively by NRU assay. Results also showed that PO and PS exposed cells reduced the normal morphology and adhesion capacity of HepG2 cells. HepG2 cells exposed with $50{\mu}g/ml$ and higher concentrations of PO and PS lost their typical morphology, become smaller in size, and appeared in rounded bodies. Our results demonstrated preliminary screening of anticancer activity of Portulaca oleracea and Petroselinum sativum extracts against HepG2 cells, which can be further used for the development of a potential therapeutic anticancer agent.

• Journal of Life Science
• /
• v.29 no.10
• /
• pp.1136-1143
• /
• 2019

The purpose of this study was to investigate the biological activities of an aqueous extract of Angelica gigas (Ag) fermented by Saccharomyces cerevisiae (Sc). First, the soluble solids of the F/3 group, in which the Ag was fermented by Sc for 3 days, decreased from $1^{\circ}Bx$ to $0.9^{\circ}Bx$. On the other hand, the pH increased with the number of days of fermentation. The result of a TLC experiment confirmed that it gradually decomposed into a low-molecular weight sugar form upon fermentation. The total phenolic compounds and flavonoid contents were higher in the fermented group than in the non-fermented group. K and Ca contents were increased by fermentation in the following order: F/3, NF, and F/0 groups. Decursin and decursinol angelate contents were highest in the F/3 group. The DPPH (${\alpha}$, ${\alpha}{\prime}$-diphenyl-${\beta}$-picrylhydrazyl) radical scavenging activity of the NF, F/0, and F/3 groups were 41.89%, 39.51%, and 60.26%, respectively. The inhibition activities of tyrosinase and lipoxygenase were stronger in the F/3 group than in the NF group. This experiment showed that the fermentation of Ag Nakai can lead to an increase in its antioxidant ability, physiological activity, whitening and anti-inflammatory effects. Thus, this oriental herbal medicine can be developed into a functional material that can be utilized in the development of cosmetic products in future.