Rheumatoid arthritis (RA) is an autoimmune disease that starts with decreased tolerance to modified self-antigens and eventually leads to synovitis and destruction of bone and cartilage. Age is a risk factor for developing RA. Major changes in the immune system come with age due to chronic oxidative stress on the deoxyribonucleic acid (DNA) damage pathway, somatic mutation, modifications of auto-antigens, T cell tolerance and activation of fibroblast-like synoviocytes (FLS). Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2) suppress T cell receptor signaling. Sirtuin 1 (SIRT1) is a critical immune suppressor of T cell activation and a key regulator of oxidative stress. When oxidative stress reduces activity of SIRT1, the breakdown of tolerance to modified self-antigens is expected. Generation of ROS can be perpetuated by enhanced DNA damage and dysfunctional mitochondria in a feedback loop during the development of RA. Through major T cell loss and selective proliferation of peripheral T cells, pro-inflammatory T cell pools with abnormal features are established in the T cell compartment. Hypoxic and inflammatory condition in synovium perpetuates ROS generation, which leads to the activation of FLS. In both T cell and synovium compartment, oxidative stress reshapes the immune system into the development of pre-clinical RA.
Arthritis, Rheumatoid* ; Autoantigens ; Autoimmune Diseases ; Cartilage ; DNA ; DNA Damage ; Immune System ; Mitochondria ; NADP ; NADPH Oxidase ; Oxidative Stress ; Oxidoreductases ; Reactive Oxygen Species* ; Receptors, Antigen, T-Cell ; Risk Factors ; Sirtuin 1 ; Synovial Membrane ; Synovitis ; T-Lymphocytes

BACKGROUND: The Internet has advantages in terms of accessibility and amount of information, and the search for health information over the Internet is increasing exponentially. The purpose of this study is to analyze the information generated about some dental treatment on the internet by year. METHODS: Naver Knowledge (JisikIn in Korean) which is an interactive search service was selected as the first search site in Korea. Scaling, wisdom tooth extraction, and endodontic treatment that can be paid by Korean health insurance were selected. Finally, 4,729 questions about scaling, 23,963 wisdom teeth extraction questions and 17,733 endodontic treatment questions were extracted. The question contents, the information about the questioner and the answerer, and an error of answers were investigated. Frequency analysis was used and chi-square test was used if necessary. RESULTS: The most frequently asked questions were discomfort and dissatisfaction after the treatment. The need for treatment was the second in questions of the wisdom tooth extraction and endodontic treatment, but the health insurance benefit was the second in dental scaling. Most of the questioners didn't disclose personal information. The public answered the most in 2013~2014, but the highest percentage of the respondents was experts in 2017. Responses were mostly personal experience, but showed a tendency to decrease with years, and professional knowledge showed an increasing tendency. The error of the answer has also gradually decreased. CONCLUSION: Questions about dental care over the Internet are increasing exponentially, experts are responding increasingly, and errors in answers are decreasing. Nevertheless, it is necessary to pay attention to the related expert group to prevent misinformation.
Dental Care ; Dental Scaling ; Humans ; Insurance, Health ; Internet ; Korea ; Molar, Third ; Surveys and Questionnaires

According to WHO global estimates from 2008, more than 1.4 billion adults were overweight and among them, over 200 million men and 300 million women were obese. Although the main treatment modalities for overweight and obese individuals remain dieting and physical exercise, the synthetic anti-obesity medications have been increasingly used due to their perceived convenience. Generally, anti-obesity medications are classified as appetite suppressants or fat absorption blockers. In the present study, we examined the adverse side-effects in respect of behavior changes of phentermine and Ephedra sinica (mahuang) that are anti-obesity drugs currently distributed to domestic consumers. Phentermine is mainly classified as an anorexing agent and mahuang a thermogenic agent. Because phentermine and mahuang are considered to display effectiveness through the regulation of nerve system, their potential influences of on behavioral changes were examined employing animal experiments. From the results of experiments testing locomotor activity through the use of treadmill, rota-rod, and open field system, phentermine and mahuang were commonly revealed to induce behavioral changes of rats by reducing a motor ability, an ability to cope with an external stimulus, and a sense of balance or by augmenting wariness or excitement. These adverse effects of phenternime and mahuang in behavioral changes need to be identified in humans and anti-obesity medications such as phentermine and mahuang should be prescribed for only obesity where it is anticipated that the benefits of the treatment outweigh their potential risks.
Absorption ; Adult ; Animal Experimentation ; Animals ; Anti-Obesity Agents* ; Appetite Depressants ; Diet ; Diethylpropion ; Ephedra sinica ; Exercise ; Female ; Humans ; Male ; Models, Animal* ; Motor Activity ; Obesity ; Overweight ; Phentermine* ; Rats ; Rats, Sprague-Dawley*

Genistein is one of isoflavones mostly derived in a leguminous plant. It is well known as one of phytoestrogens that have structures similar to the principal mammalian estrogen. It has diverse biological functions including chemopreventive properties against cancers. Anticancer efficacies of genistein have been related with the epidemiological observations indicating that the incidence of some cancers is much lower in Asia, where diets are rich in soyfoods, than Western countries. This review deals with in vivo anticancer activities of genistein identified in animal studies being divided into its effects on carcinogenesis and cancer progression. Because animal studies have advantages in designing the experiments to suit the goals, they imply diverse information on the anticancer activity of genistein. The in vivo animal studies have adopted the specific animal models according to a developmental stage of cancer to prove the anticancer efficacies of genistein against diverse types of cancer. The numerous previous studies insist that genistein effectively inhibits carcinogenesis in the DMBA-induced animal cancer models by reducing the incidence of adenocarcinoma and cancer progression in the transgenic and xenograft animal models by suppressing the tumor growth and metastatic transition. Although the protective effect of genistein against cancer has been controversial, genistein may be a candidate for chemoprevention of carcinogenesis and cancer progression and may deserve to be the central compound supporting the epidemiological evidence.
Adenocarcinoma ; Animals ; Asia ; Carcinogenesis ; Chemoprevention ; Diet ; Estrogens ; Genistein* ; Heterografts ; Incidence ; Isoflavones ; Mice ; Mice, Transgenic ; Models, Animal* ; Phytoestrogens ; Plants

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.