Preventive empagliflozin activity on acute acetic acid-induced ulcerative colitis in rats via modulation of SIRT-1/PI3K/AKT pathway and improving colon barrier.

BACKGROUND: Ulcerative colitis (UC) is a chronic colon inflammation that is linked to exposure to environmental factors leading to improper immune responses to enteric microbes in genetically susceptible individuals. This study was designed to explore the possible protective impact of Empagliflozin (EMPA), an anti-diabetic sodium-glucose cotransporter-2 (SGLT2) inhibitor, on acetic acid (AA)-induced UC in rats. METHOD: Intrarectal instillation of AA (2 ml, 3% v/v) was used to induce UC. EMPA (10 & 30 mg/kg) was administered orally for 11 days. RESULTS: EMPA successfully counteracted AA-induced UC that was manifested by improving colonic histopathological architecture concomitant with a marked decrease in disease activity index (DAI), colon weight, weight/length ratio, serum lactate dehydrogenase (LDH) activity, and C-reactive protein (CRP) level. Additionally, EMPA successfully restored the disrupted oxidant/antioxidants balance induced by AA. Moreover, EMPA significantly induced silent information regulator-1(SIRT-1) expression along with a significant reduction in phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT), nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF)-α and interleukins (IL-1ß and IL-6) expression in colonic tissues. Furthermore, EMPA successfully improved the colonic barrier that was appeared from the marked induction of tight junction proteins level (occludin and claudin-1). CONCLUSION: EMPA successfully counteracted AA-induced UC in rats via the modulation of SIRT1/PI3K/AKT/NF-κB inflammatory pathway, normalizing oxidant/antioxidants balance, and improving the integrity of colon barrier.

Antibacterial and Biofilm-Preventive Photocatalytic Activity and Mechanisms on P/F-Modified TiO2 Coatings.

Photocatalytic antibacterial and biofilm-preventive activity in liquid of heavy-metal-free coatings based on a phosphorus (P)- and fluorine (F)-modified TiO2 photocatalyst has been investigated. They reveal significantly higher immediate and longer-term (biofilm-preventive) inactivation capacity than a reference coating made of the commercial photocatalyst TiO2 P25 on three bacterial species differing in cell wall type and ability to resist oxidative stress (Escherichia coli, Staphylococcus epidermidis, Pseudomonas fluorescens) (up to more than 99% reduction of colonization on P/F-modified TiO2 coating compared to about 50% on P25 TiO2 coating for 10 min UV-A illumination). This results from the P- and F-induced improvement of photocatalyst properties and from the smoother surface topography, which shortens reactive oxygen species (ROS) diffusion to the outer membrane of the targeted adhered bacteria. Decrease in ROS-related impairment of cell wall, respiratory, and enzymatic activities confirms the loss of ROS throughout the bacterial cell degradation. Staphylococcus epidermidis and Pseudomonas fluorescens are less sensitive than Escherichia coli, with a probable relation to the bacterial oxygen stress defense mechanism. The coating antibacterial efficacy was highly affected by phosphate ions and the richness in dissolved oxygen of the reaction medium.

Allergy-preventive effects of linarinic acid and its tetrahydropyrrolo[2,1-b]quinazoline derivatives isolated from Linaria vulgaris.

Linarinic acid, (-)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid (4a), was isolated from the ethanol extract of Linaria vulgaris Mill. In our previous study, a series of tetrahydropyrrolo[2,1-b]quinazoline derivatives 4b, 4c, 5a, 5b, 6a and 6b that were structurally related to 4a and evaluated as neuroprotective agents were synthesized. The aim of the present study was to investigate the novel features of these compounds. We examined their allergy-preventive effects using an in vivo assay system we developed previously, that monitors a decrease in blood flow in the tail vein of mice subjected to sensitization with hen egg-white lysozyme. We observed that 4a and its three derivatives, amide (6a), ester (5a), bromine (4b), and alcohol substituent (6b), showed significant allergy-preventive activities. The study confirmed the allergy-preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by comprehensively monitoring the specific blood flow decrease occurring in the induction phase of allergy. This finding may aid in the development of new agents for the treatment of allergic diseases such as atopic dermatitis, allergic asthma, and hay fever.

Evaluation of fungicides enestroburin and SYP1620 on their inhibitory activities to fungi and oomycetes and systemic translocation in plants.

Enestroburin and SYP1620 are newly developed strobilurin chemicals carrying fungicidal activity and need to be fully characterized in activities of anti-oomycete or anti-fungi, disease prevention and systemic translocation in planta. Their inhibitory activities were examined by amending the chemical in agar media, on which selected plant pathogens were grown and mycelial growth were measured. Effective concentrations for 50% inhibition (EC50) of mycelial growth were calculated to determine the level of fungicide sensitivity of the pathogen. Azoxystrobin was used as control. To examine the prevention and systemic translocation in plants, the fungicides were either sprayed on wheat leaves or dipped on wheat roots, which then were detected using high performance liquid chromatography. All the three fungicides inhibited mycelial growth of Sphacelotheca reiliana, Phytophthora infestans, Peronophythora litchi, and Magnaporthe oryzae, with EC50 values ranging from 0.02 to 2.84µg/ml; EC50 of SYP1620 was significantly lower than that of azoxystrobin and enestroburin on Valsa mali, Gaeumannomyces graminis, Alternaria solani, and Colletotrichun orbiculare. The three QoI fungicides showed strong inhibitory activities on spore germination against the 13 pathogens tested and were highly effective on biotrophic pathogens tested. Enestroburin and SYP1620 penetrated and spread in wheat leaves, but the penetration and translocation levels were lower compared to azoxystrobin. The three fungicides were all rapidly taken up by wheat roots and transported upwards, with greater fungicide concentrations in roots than in stems and leaves. The results indicate that enestroburin and SYP1620 are systemic fungicides that inhibit a broad spectrum of fungi and oomycetes.

Addiction research centres and the nurturing of creativity: the Kurihama medical and addiction centre-a profile.

The Kurihama Medical and Addiction Center began to conduct research and to provide medical care for alcohol-related problems in 1963, when special alcoholism treatment wards were established in Japan for the first time. At first, the provision of medical care to patients was prioritized. However, training courses for specialists were initiated in 1975, and the Department of Clinical Research was established in 1984, which led to the formation of the present management structure in which the centre's staff are shared by three departments: Medical Care, Clinical Research and Education and Information. The Department of Medical Care provides specialized treatment for alcohol use disorders and medical services for other conditions, including behavioural addictions such as internet addiction and gambling disorder, as well as dementia and other psychiatric disorders. The Departments of Clinical Research and Education and Information are engaged mainly in specialized activities related to alcohol. The Department of Clinical Research conducts research on the epidemiology of alcohol use, the effects of alcohol on health and the treatment of alcohol use disorders in Japan, in cooperation with universities and other research institutions. The Department of Education and Information fosters the human capacity to achieve the primary, secondary and tertiary prevention of alcohol-related problems and the dissemination of information on alcohol. The centre also performs alcohol-related problem prevention activities, government consultations and international collaborative research and personal exchanges, thereby functioning as a central institution for alcohol policy-based medical services and research in Japan.

Evaluation on implementation of preventive activities of non-communicable diseases / Монголын Анагаах Ухаан

Background: Mongolia is one of the most influenced countries by non-communicable diseases among developing countries. Non-communicable diseases, including cardiovascular diseases, cancers, respiratory diseases, diabetes, and injuries have become the major causes of morbidity and mortality in Mongolia.Goal: To assess impact of preventive intervention activities of non-communicable diseases in framework of the Millennium challenge account (MCA) health projectMethods: We conducted 17 focus group discussions (FGD) from March to April 2013 in primary and secondary health care settings, of which six in urban and eleven in rural areas.We identified themes concerning the current situation of NCD related health services from the perspective of health professionals, and insights into institutional and professional experiences related to management, implementation and coordination of the newly implemented MCA-Mongolia NCD prevention and control project.Results: As a result of the health project, NCD related knowledge and skills of health professionals have improved through progressive training, and development of guidelines and manuals. During the project, availability of equipment supplies has improved. Accordingly, medical equipment and laboratory reagents needed for early detection of NCDs were provided to primary and secondary health care settings, despite some challenges in the implementation of the project. As result of theproject implementation, increased public awareness on NCDs, and attitude change were considered as the biggest changes.Conclusion: The health project was considered as successful to provide knowledge on the best practice in NCD prevention.

Mycalamide A shows cytotoxic properties and prevents EGF-induced neoplastic transformation through inhibition of nuclear factors.

Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P(+) cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed.

Bioactive hydroperoxyl cembranoids from the Red Sea soft coral Sarcophyton glaucum.

A chemical investigation of an ethyl acetate extract of the Red Sea soft coral Sarcophyton glaucum has led to the isolation of two peroxide diterpenes, 11(S) hydroperoxylsarcoph-12(20)-ene (1), and 12(S)-hydroperoxylsarcoph-10-ene (2), as well as 8-epi-sarcophinone (3). In addition to these three new compounds, two known structures were identified including: ent-sarcophine (4) and sarcophine (5). Structures were elucidated by spectroscopic analysis, with the relative configuration of 1 and 2 confirmed by X-ray diffraction. Isolated compounds were found to be inhibitors of cytochrome P450 1A activity as well as inducers of glutathione S-transferases (GST), quinone reductase (QR), and epoxide hydrolase (mEH) establishing chemo-preventive and tumor anti-initiating activity for these characterized metabolites.

The Cancer-preventive Potential of Panax ginseng: A Review of Human and Experimental Evidence / 예방의학회지

OBJECTIVE: We have reviewed the potential cancer preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in oriental countries. DATA IDENTIFICATION AND STUDY SELECTION: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-2000) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were also considered. RESULTS: Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.