Molecular hydrogen protects against oxidative stress‑induced RAW 264.7 macrophage cells through the activation of Nrf2 and inhibition of MAPK signaling pathway

Rahima Begum,Cheol‑Su Kim,Ailyn Fadriquela,Johny Bajgai,Xingyu Jing,Dong‑Heui Kim,Soo‑Ki Kim,Kyu‑Jae Lee 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.2

Background Oxidative stress is involved in the development of many inflammatory, metabolic and aging diseases. Objective In this study we investigated, the protective effects of H2 on RAW 264.7 macrophage cell against LPS-and H2O2- induced oxidative stress by the inhibition of MAPK pathway and also activate the Nrf2 pathway. Results Our results showed H2 increased the macrophage cell proliferation and generated ROS and NO against LPS stimulation to exert an active immune response. Similarly, H2 protected the macrophage cell from H2O2- induced oxidative stress. H2 reduced the LPS-and H2O2- induced inflammatory cytokine production and intracellular calcium influxes. H2 inhibited the LPS-and H2O2- induced phosphorylation of MAPK pathway and its downstream signaling molecules. Furthermore, H2 protected the macrophage cell from mitochondrial apoptosis. H2 increased Nrf2 protein expression indicating its strong anti-oxidative effects against oxidative stress. Conclusion Collectively, our results indicate the strong antioxidant role of H2 against LPS-and H2O2- induced oxidative stress on macrophage cells by activating the Nrf2 pathway and inhibiting the MAPK-signaling pathway.

Antibacterial Effects of Hydrogen Water on Human Pathogenic Bacteria

Rahima Begum,Cheol-Su Kim,Ailyn Fadriquela,Johny Bajgai,Soo-Ki Kim,Kyu-Jae Lee 한국물학회 2019 한국물학회지 Vol.7 No.1

Hydrogen water (HW) produced by electrolysis of water has characteristics of extremely low oxidation-reduction potential (ORP) value and high dissolved hydrogen (DH). It has been proved to have various beneficial effects including anti-oxidantion and anti-inflammation however, the antibacterial effect on human pathogenic bacteria is poorly studied. In the present study, we investigated the antibacterial effects of hydrogen water on three different types of human pathogenic bacterial species, such as Staphylococcus aureus, Escherichia coli, and S. mutans. S. aureus, S. mutans, and E. coli were cultured and diluted with hydrogen water and tap water at different ratio (9:1, 5:5 and 1:9) and inoculated on Brain Heart Infusion (BHI) and Mac Conkey agar. After inoculation, the S. aureus, E. coli culture plates were incubated at 37 ℃ in aerobic condition for 24 h, S. mutans in anaerobic condition for 48 hours. After 24 h of incubation, the total number of the colony was measured as CFU/mL. We found that the number of all three bacterial species was fully reduced at the ratio of 1:9 hydrogen water, but the tap water had no effects. We can conclude from our results, that hydrogen water may have positive and strong antibacterial effects on various human pathogenic bacteria. But, it needs other experiments to clarify the antimicrobial effects of hydrogen water.

Hair Growth Promoting Effects of Mineral-rich Spring Water in SKH-1 Hairless Mice

Rahima Begum,Jesmin Ara,Md Faruk Ahmed,Johny Bajgai,Ailyn Fadriquela,Kyu Jae Lee 한국물학회 2017 한국물학회지 Vol.6 No.1

Mineral rich spring water has been used in spa and bathing purpose that often belong to traditional medicinal therapies. It also considered as a classical alternative medicine to cure the immunological disease. Recently, mineral rich containing medicine and cosmetics has been widely applied in hair loss purpose but not tried by mineral water. Therefore, the purpose of the present study is to observe the hair growth promoting effects of mineral rich spring water in SKH-1 hairless mice. We designed this study to evaluate the mineral water has hair growth promoting effect. The experimental SKH-1 hairless mice were divided into a normal control group (NC: No treatment), a positive control group (M: 3% Minoxidil), and different concentrations of mineral water group as a treatment group (MW: 2.5%, 5%, and 10%). All the test samples were topically sprayed on the three distinct parts of the leg, dorsal and a shoulder portion (about 1 cm2 areas) of the mice skin (100 L per application), twice a day, for μ 21 days. The number of hair and length was measured by taking a photograph of using the scale bar tools of the DinoCapture 2.0 digital microscope windows software. The thickness of the hair was measured by using scanning electron microscope. After 21 days of the experiment, mice treated with 2.5% mineral water showed the preferable effect on the number of hair, length, and thickness compared to the PC group and other concentration groups. However, the positive control minoxidil has no mineral containing ingredient but it has strong activity in hair growth. In our study, we found minoxidil had shown less active in hair growth effects in SKH-1 hairless mice. These results suggest that the using of optimum concentration of mineral rich spring water might have a remarked hair growth promoting effect, as observed morphologically. Collectively, according to our studies, we hypothesized that the topical application of mineral rich spring water might represent a novel strategy for the management and therapy for hair falling purpose. However, furthermore, studies could be more assured this hair growth promoting effects.

Anti-obesity Effect of Whole Body Vibration Exercise : A Clinical Pilot Trial

Ailyn Fadriquela,Johny Bajgai,Rahima Begum,Jing Xingyu,Cheol Su Kim,Soo-Ki Kim,Dong Heui Kim,Kyu-Jae Lee 한국물학회 2019 한국물학회지 Vol.7 No.1

It is well known that exercise is effective in overcoming obesity. Recent studies have focused on various types of exercise in which vibration exercise was involved. In this study, we investigated the effect of whole body vibration (WBV) exercise using the bed-type vibrator through pre-post data analysis. Twenty participants were carefully recruited and were treated on a vibrating bed with an automatic program developed by integration of 1-8 steps for 1 hr maintaining the 40°C of bed temperature. Blood pressure, body mass indices (BMI), hematological indices, oxidative stress-related markers, cytokines, and obesity-related biomarkers such as adiponectin, resistin and irisin were measured. Results showed that diastolic blood pressure was significantly lowered after 1 hr of WBV treatment (p < 0.05). In lipid tests, total cholesterol and low-density lipoprotein cholesterol were decreased (p < 0.01, respectively). Oxidative stress-related markers such as reactive oxygen species (p < 0.05), nitric oxide (p < 0.05) and glutathione peroxidase (p < 0.01) were significantly increased. Interleukin (IL)-10, and tumor necrosis factor-α were significantly decreased and IL-6 and interferon (INF)-γ also showed decreasing trend. Adiponectin involved in insulin sensitivity was increased and resistin involved in insulin resistance decreased, but there were no significance. In addition, irisin levels were significantly decreased after the WBV exercise. In conclusion, the bed-type of WBV exercise reduced the blood pressure and cholesterol, and showed favorable response to obesity biomarkers. Also, oxidative stress level was increased but relatively stable and not severe, and inflammation and allergic reaction were not observed. Thus, the application of bed-type WBV exercise can be a safe and effective alternative for the improvement of obesity.

Effect of the Mineral Complex Treatment on Atopic Dermatitis like-Lesion in 2, 4-Dinitrochlorobenzene Induced in Hairless Mice

Johny Bajgai,Cheol-Su Kim,Ailyn Fadriquela,Rahima Begum,Xingyu Jing,Dong Heui Kim,Soo-Ki Kim,Kyu-Jae Lee 한국물학회 2019 한국물학회지 Vol.7 No.1

Atopic dermatitis (AD) is chronic relapsing skin inflammatory allergic disease characterized by a complex pathogenesis including skin barrier dysfunction, immune-redox disturbances and pruritus. Topical treatment medications such as corticosteroids, calcineurin inhibitors, T-cell inhibitors were used in AD but these agents may have some potential side-effects. Therefore, many researchers explored abundant numbers of alternative therapies by using natural products and mineral compounds related with its antioxidant and immunomodulator effects to minimize toxicity and adverse-effects. In the present study, we investigated the effects of mineral complex material patch (MCM) treatment on AD-like lesions in 2, 4-dinitrochlorobenzene (DNCB)-induced hairless mice. Animals were divided into four groups; normal control, negative control (DNCB Only), DNCB+ Tacrolimus (PC) and DNCB+MCM patch to evaluate its therapeutic effect on DNCB-induced AD. Our results showed that MCM patch improved the skin dermatitis by significantly increasing the skin barrier strength, score and moisture level and decreasing the transepidermal water loss as compared to DNCB only group. In line, ROS level, inflammatory, Th1 and Th2 cytokines were decreased with MCM treatment whereas nitric oxide level and total anti-oxidant enzyme activities were significantly enhanced as compared to DNCB only and NC groups. Moreover, total IgE level was significantly increased in DNCB only group and decreased in PC and MCM treated group. Taken together, our findings suggest that MCM may potentially protect against AD lesional skin via regulation of skin barrier function and immune-redox response. However, further studies are needed to explain the detail molecular mechanism of MCM effect.

RUNX1 Dosage in Development and Cancer

Lie-a-ling, Michael,Mevel, Renaud,Patel, Rahima,Blyth, Karen,Baena, Esther,Kouskoff, Valerie,Lacaud, Georges Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.2

The transcription factor RUNX1 first came to prominence due to its involvement in the t(8;21) translocation in acute myeloid leukemia (AML). Since this discovery, RUNX1 has been shown to play important roles not only in leukemia but also in the ontogeny of the normal hematopoietic system. Although it is currently still challenging to fully assess the different parameters regulating RUNX1 dosage, it has become clear that the dose of RUNX1 can greatly affect both leukemia and normal hematopoietic development. It is also becoming evident that varying levels of RUNX1 expression can be used as markers of tumor progression not only in the hematopoietic system, but also in non-hematopoietic cancers. Here, we provide an overview of the current knowledge of the effects of RUNX1 dosage in normal development of both hematopoietic and epithelial tissues and their associated cancers.

Effectiveness of Mavrilimumab in Viral Infections Including SARS-CoV-2 Infection - A Brief Review

Bhatt Kinal,Garimella Radhika,Taugir Rahima,Mehta Isha,Jamal Muhammad,Vijayan Rupalakshmi,Offor Rita,Nwankwo Kanayo,Arif Uroosa,Waheed Khurram,Kumari Priyanka,Lathiya Maulik,Michel George,Pandya Naush 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.1

Hyperinflammation and cytokine storm has been noted as a poor prognostic factor in patients with severe pneumonia related to coronavirus disease 2019 (COVID-19). In COVID-19, pathogenic myeloid cell overactivation is found to be a vital mediator of damage to tissues, hypercoagulability, and the cytokine storm. These cytokines unselectively infiltrate various tissues, such as the lungs and heart, and nervous system. This cytokine storm can hence cause multi-organ dysfunction and life-threatening complications. Mavrilimumab is a monoclonal antibody (mAb) that may be helpful in some cases with COVID-19. During an inflammation, Granulocyte-macrophage colony-stimulating factor (GM-CSF) release is crucial to driving both innate and adaptive immune responses. The GM-CSF immune response is triggered when an antigen attaches to the host cell and induces the signaling pathway. Mavrilimumab antagonizes the action of GM-CSF and decreases the hyperinflammation associated with pneumonia in COVID-19, therefore strengthening the rationale that mavrilimumab when added to the standard protocol of treatment could improve the clinical outcomes in COVID-19 patients, specifically those patients with pneumonia. With this review paper, we aim to demonstrate the inhibitory effect of mavrilimumab on cytokine storms in patients with COVID-19 by reviewing published clinical trials and emphasize the importance of extensive future trials.

Balneotherapeutic effects of high mineral spring water on the atopic dermatitis-like inflammation in hairless mice via immunomodulation and redox balance

Johny Bajgai,Ailyn Fadriquela,Jesmin Ara,Rahima Begum,Md Faruk Ahmed,Cheol-Su Kim,Soo-Ki Kim,Kwang-Yong Shim,Kyu-Jae Lee 한국물학회 2017 한국물학회지 Vol.6 No.1

Atopic dermatitis (AD) is a chronic relapsing allergic inflammatory skin disease that currently affects millions of children and adults worldwide. Drugs used to treat these inflammatory diseases include anti-histamines, corticosteroids and calcineurin inhibitors but these drugs have their limitations such as adverse effects with their long-term usage. Thus, researcher’s interest in several alternative and complementary therapies are continually growing and balneotherapy is one of these approaches. Therefore, we investigate the bathing effect of high concentration mineral spring water (HMW) on redox balance and immune modulation in 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis like inflammation in hairless mice. We induced AD-like inflammation by application of DNCB on the dorsal skin of female skh-1 hairless mice. The mice were treated with 100% pure HMW (PHMW) and 10% diluted HMW (DHMW) through bathing once a day for 4 weeks. Tacrolimus ointment (0.1%) was used as positive control (PC) and only DNCB treatment as negative control (NeC) group. The severity of skin lesion inflammation was assessed through clinical scoring and observing scratching behavior. Levels of immunoglobulin E (IgE) and inflammatory cytokines in serum were detected by ELISA and multiplex bead array system, and the levels of oxidative stress-related biomarkers and antioxidant enzyme were also measured. We found that HMW significantly decreased the scratching behavior in PHMW and DHMW groups at the 2nd week and in PHMW group at 4th week compared to NeC group. Likewise, serum IgE level was significantly decreased in DHMW group as compared to NeC group. In line, the level of inflammatory cytokines in serum such as interleukin (IL)-1 , IL-13 and tumor necrosis factor- β α were significantly inhibited in PHMW and DHMW groups compared to NeC group. In parallel, total reactive oxygen species (ROS) of serum level was significantly decreased in PHMW treatment groups compared to NeC group. Consistently, serum malondialdehyde (MDA) level in PHMW group was lower than in NeC group. By contrast, glutathione peroxidase (GPx) activity was significantly enhanced in PHMW than NeC. Collectively, our study indicates a balneotherapeutic effect of HMW on DNCB-induced AD like inflammation in hairless mice via immunomodulation and redox balance.

Expression of Toll-like Receptor 9 Increases with Progression of Cervical Neoplasia in Tunisian Women - A Comparative Analysis of Condyloma, Cervical Intraepithelial Neoplasia and Invasive Carcinoma

Fehri, Emna,Ennaifer, Emna,Ardhaoui, Monia,Ouerhani, Kaouther,Laassili, Thalja,Rhouma, Rahima Bel Haj,Guizani, Ikram,Boubaker, Samir Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.

Anti-Inflammatory Effect of Rosa rugosa Flower Extract in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

Xirali Tursun,Yongxin Zhao,Zulfiya Talat,Xuelei Xin,AdilaTursun,Rahima Abdulla,Haji AkberAisa 한국응용약물학회 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.2

Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the antiinflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and interleukin 1β (IL-1β), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-κB) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.