Suppression and mitigation
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OBJECTIVE: The effect of the immunosuppressive fraction of boar seminal vesicle fluid (ISF) was tested on the manifestation of adjuvant arthritis (AA) in rats. METHODS: The inhibitory effect of ISF on mitogen-stimulated proliferation of rat lymphocytes was evaluated by immunoassay using bromodeoxyuridine incorporation. Adjuvant arthritis was induced in male Long Evans rats with Mycobacterium butyricum in adjuvant. ISF was administered at the time of the induction of arthritis. At the time of maximal manifestation of the disease, the hind paw swelling and thymus weight were estimated. IgM and IgG in the rat blood sera were quantified by sandwich ELISA. Serum corticosterone was analyzed by radioimmunoassay. Serum NO2-/NO3-were estimated by diazotation. Serum albumin was measured spectrophotometrically. The expression of IL-6 mRNA in peritoneal macrophages was estimated by dot-blot hybridization. RESULTS: Treatment of arthritic rats with ISF attenuated hind paw edema. The production of IgG subclasses dropped in ISF-treated AA rats. The thymus mass and serum albumin concentration were partially restored due to the ISF treatment. Serum corticosterone as well as NO2-/NO3- concentrations were reduced by the ISF effect. The expression of IL-6 in peritoneal macrophages was inhibited in AA rats after ISF treatment. CONCLUSION: ISF attenuated the manifestation of AA in rats and mitigated the inflammation. Immunoglobulin production was most probably inhibited by the decreased proliferation of B lymphocytes.
- MeSH
- artritida experimentální * farmakoterapie imunologie MeSH
- dusičnany krev MeSH
- dusitany krev MeSH
- exprese genu imunologie MeSH
- imunoglobulin G krev MeSH
- imunoglobulin M krev MeSH
- imunosupresiva farmakologie imunologie MeSH
- injekce intraperitoneální MeSH
- interleukin-6 genetika MeSH
- kortikosteron krev MeSH
- krysa rodu rattus MeSH
- messenger RNA analýza MeSH
- peritoneální makrofágy imunologie účinky léků MeSH
- potkani Long-Evans MeSH
- potkani Wistar MeSH
- prasata MeSH
- proteiny semenné plazmy MeSH
- proteiny farmakologie imunologie MeSH
- sérový albumin MeSH
- sperma chemie imunologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
This study was to evaluate the efficacy of TOXO-XL (XL), an integrated mycotoxin-mitigating agent, on aflatoxin B1 (AFB1)-induced damage in Leghorn male hepatoma (LMH), porcine jejunum epithelial cell line (IPEC-J2) and porcine alveolar macrophages (3D4/21) cells, and to explore its potential mechanisms. The results showed that 30% inhibition concentration (IC30) of AFB1 in LMH, IPEC-J2 and 3D4/21 cells was 0.5, 15.0, and 2.5 mg/L, respectively. Notably, cell viability, ROS, apoptosis and DNA lesion induced by AFB1 (IC30) could be ameliorated by the supplementation with XL at the dosage of 0.025, 0.025 and 0.005%, respectively. Additionally, the migration and phagocytosis abilities impaired by AFB1 were also restored by XL in 3D4/21. Further experiments revealed that XL supplementation markedly attenuated AFB1-induced inflammatory response by decreasing IL-1β, IL-6 and IL-10 in LMH, IL-6 in IPEC-J2 and IL-1β in 3D4/21 cells. Meanwhile, XL supplementation reversed the alterations of BAX, BCL-2 and caspase-3 induced by AFB1 in the three cells, suggesting that AFB1-induced apoptosis may be suppressed via the mitochondria-dependent pathway. Furthermore, XL may have a protective effect on the intestinal barrier through the restoration of occludin protein. Conclusively, these findings indicated that XL could alleviate AFB1-induced cytotoxicity in the three cells, potentially through the regulation of cytokines, ROS, apoptotic and DNA damage signaling.
- MeSH
- aflatoxin B1 toxicita metabolismus MeSH
- apoptóza MeSH
- epitelové buňky MeSH
- hepatocelulární karcinom * metabolismus MeSH
- interleukin-6 metabolismus MeSH
- kur domácí metabolismus MeSH
- nádory jater * metabolismus MeSH
- prasata MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.
- MeSH
- apoptóza účinky léků MeSH
- buněčná adheze * účinky léků MeSH
- difúzní velkobuněčný B-lymfom * farmakoterapie patologie MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- protoonkogenní proteiny c-jun metabolismus genetika MeSH
- pyruváty * farmakologie terapeutické užití MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cholestatic liver diseases are characterized by intrahepatic accumulation of bile acids (BAs), exacerbating liver inflammation, and fibrosis. Dimethyl fumarate (DMF) is a clinically approved anti-inflammatory drug that demonstrated protective effects in several experimental models of liver injury. Still, its effect on BA homeostasis and liver fibrosis has not been thoroughly studied. Herein, we hypothesized that DMF could improve BA homeostasis and mitigate the progression of cholestasis-induced liver fibrosis. The DMF was administered to mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholestasis for 4 wk. The content of individual BAs in the plasma, liver, bile, intestine, and feces was measured using the LC-MS method alongside the analysis of liver phenotype and related executive and regulatory pathways. The DMF slowed down the progression of DDC-induced liver fibrosis by suppressing hepatic stellate cell and macrophage activation and by reducing c-Jun N-terminal kinase phosphorylation. Notably, DMF reduced BA cumulation in the plasma and liver of cholestatic mice by increasing BA fecal excretion via their reduced Bacteroidetes phyla-mediated deconjugation in the intestine. In addition, DMF was identified as the antagonist of the mouse farnesoid X receptor in enterocytes. In conclusion, DMF alleviates DDC-induced cholestatic liver injury through pleiotropic action leading to significant anti-inflammatory and antifibrotic activity of the agent. In addition, DMF mitigates BA retention in the liver and plasma by increasing their fecal excretion in cholestatic mice. These findings suggest that DMF warrants further investigation as a potential therapeutic agent for human chronic fibrosing cholestatic liver disorders.NEW & NOTEWORTHY Chronic cholestatic cholangiopathies present a therapeutic challenge due to their complex pathophysiology, where the accumulation of bile acids plays a crucial role. In this study, we found that dimethyl fumarate attenuated cholestatic liver damage in a murine model through its significant anti-inflammatory and antifibrotic activity supported by reduced bile acid accumulation in the plasma and liver via their increased fecal excretion.
- MeSH
- cholestáza * farmakoterapie metabolismus chemicky indukované MeSH
- dimethyl fumarát * farmakologie terapeutické užití MeSH
- jaterní cirhóza * metabolismus farmakoterapie patologie etiologie MeSH
- jaterní hvězdicovité buňky účinky léků metabolismus MeSH
- játra * metabolismus účinky léků patologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- žlučové kyseliny a soli * metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Kůže hraje významnou roli v nespecifické i specifické imunitní obraně vůči iritanciím, mikrobům a alergenům, projevují se zde ale i reakce autoimunitní a autoinflamatomí. Nalezneme zde projevy všech dosud popsaných alergických, resp. imunitních reakcí, zejména polékové reakce JSOU ilustrativní. Stěžejní mezioborovou dermato-alergologickou jednotku představuje atopická dermatitida. Nárůst v populaci je vysvětlován nejen hygienickou, ale recentně i hapténovou hypotézou. Počátkem atopického pochoduje narušená kožní bariéra jako místo primární senzibilizace, k níž se později pridává další senzibilizace v dýchacích cestách. K dlouhodobému zvládání atopické dermatitidy, a tak i zmírnění atopického pochodu, je třeba pravidelně a individualizované o kůži pečovat, snižovat mikrobiální kolonizaci kůže a sliznic a tlumit zánět správným používáním lokálních kortikoidů či imunomodulátorů. Z hlediska prevence provokačních faktorů hrají podstatně větší roli vlivy iritační než alergické. Z alergenů jsou pak pro průběh významnější alergeny mikrobiální a kontaktní než potravinové či vzdušné.
Skin plays an important role in innate and adaptive immunity defense against the irritants, microbs and allergens, but also aut oimmune and autoinflammatory reactions are occurring here. All forms of allergic/immune reactions, that have been descripted tilll now, can be seen here and especially drug reactions are of illustrative value. Atopic dermatitis represents a pivotal interdisciplinary dermato-allergolo gic entity. The increase in population has been explained not only by the hygienic, but recently by the hapten hypothesis. At the very begginning of ato pic march there is the disrupted skin barrier as a place of primary sensitization with following later sensitization in airways. For longterm m anagement of atopic dermatitis and thus the mitigation of atopic march it is necessary to do the proper skincare regularly and in an individualized way, to reduce the microbial colonization of skin and mucosa and to suppress the inflammation by correct use of topical corticosteroids and immuno modulators. As to the prophylaxis of triggering factors - the irritative play a greater role than the allergic ones. Among the allergens im portant for the course of disease the microbial and contact allergens seem to be more important than the food or airborn.
- Klíčová slova
- polékové reakce,
- MeSH
- alergie etiologie imunologie prevence a kontrola MeSH
- atopická dermatitida etiologie imunologie terapie MeSH
- bronchiální astma imunologie MeSH
- imunita MeSH
- léková alergie MeSH
- léková dermatitida imunologie MeSH
- lidé MeSH
- péče o kůži MeSH
- rizikové faktory MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
... blood tightly regulate thrombin generation, but additional anticoagulant agents may be necessary to suppress ... ... pathologic mechanisms are elucidated, a universal definition and strategies for the prevention and/or mitigation ...
Hematology/oncology clinics of North America, ISSN 0889-8588 vol. 21, no. 1, February 2007
xvii, 1-206 s. : il. ; 24 cm
Agent-based models (ABMs) are one of the main sources of evidence for decisions regarding mitigation and suppression measures against the spread of SARS-CoV-2. These models have not been previously included in the hierarchy of evidence put forth by the evidence-based medicine movement, which prioritizes those research methods that deliver results less susceptible to the risk of confounding. We point out the need to assess the quality of evidence delivered by ABMs and ask the question of what is the risk that assumptions entertained in ABMs do not include all the key factors and make model predictions susceptible to the problem of confounding.
- MeSH
- COVID-19 epidemiologie MeSH
- lidé MeSH
- pandemie * MeSH
- SARS-CoV-2 fyziologie MeSH
- systémová analýza * MeSH
- teoretické modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Rooibos (Aspalathus linearis Brum. f) can directly influence female reproduction, but whether rooibos can influence the response of ovarian cells to FSH and whether the rooibos effects are due to the presence of quercetin remain unknown. We compared the influence of rooibos extract and quercetin (both at 10 μg/ml-1) on porcine ovarian granulosa cells cultured with and without FSH (0, 1, 10 or 100 ng/ml-1). The expression of intracellular proliferation (PCNA, cyclin B1) and apoptosis (bax, caspase 3) markers in the cells was detected by immunocytochemistry. The release of progesterone (P), testosterone (T) and estradiol (E) were evaluated with ELISAs. Administration of both rooibos and quercetin reduced the accumulation of proliferation markers and promoted the accumulation of apoptosis markers and the release of T and E. Rooibos stimulated, but quercetin inhibited, P output. Administration of FSH increased the accumulation of proliferation markers, decreased the accumulation of apoptosis markers, promoted the release of P and T, and had a biphasic effect on E output. The addition of both rooibos and quercetin mitigated or prevented the main effects of FSH. The present observations suggest a direct influence of both rooibos and quercetin on basic ovarian functions - proliferation, apoptosis, steroidogenesis and response to FSH. The similarity in the major effects of rooibos and its constituent quercetin indicates that quercetin could be the molecule responsible for the main rooibos effects on the ovary. The potential anti-reproductive effects of rooibos and rooibos constituent quercetin, should be taken into account in animal and human nutrition.
- MeSH
- Aspalathus * MeSH
- estradiol farmakologie MeSH
- folikuly stimulující hormon MeSH
- lidé MeSH
- ovarium * MeSH
- prasata MeSH
- quercetin farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chemická eliminace prachových roztočů patří mezi metody snižování alergenů v domácnostech. Stále však chybí souhrnná komparativní validační studie porovnávající účinnost současně dostupných insektícidních a akaricidních přípravků na prachové roztoče. V této studii byla festována účinnost 26 formulací biocidních pesticidních prostředků na prachové roztoče Deramaíophagoidespteronyssimus s cílem zjistit, zda jde tyto prostředky využít v eliminaci těchto roztočů a tím snížení úrovně alergenů. Experimenty byly provedeny v plastových komůrkákách pokrytých filtračním papírem impregnovaným účinnou látkou biocidu. Byla zjišťována mortalita roztočů po 24hodinové expozici. Data byla vyhodnocena pomocí probitové analýzy a byly stanoveny dávky LD99 (tj. koncentrace účinné látky, kde dochází k 99% mortalitě roztočů). Jako účinné byly zjištěny následující formulace: Acarosan®duo, AUergofif 200 SC, Biolit Plus, Cascade 5 EC, Crackdown Rapide, Fedorex-Profi, Omite 570 EW, Reslin 25 SE, Sanmite 20 WP, Vertimec 1,8 EC. Z těchto biocidů jsou Acarosan®duo, Biolit Plus, Allergoff 200 SC a Fpedorex-Profil,Omite 570 EW, Reslin 25 SE, Sanmite 20 WP, Vertimec 1,8 EC. Z těchto biocidů jsou Acarosan®duo, Biolit Plus, Allergofr200 SC a Fedorex-Profi cílené na prachové roztoče.
The chemical elimination of dust mites as allergen producers belongs to the important methods of allergen mitigation in househo lds. Up to present time, the comparison of the efficacy of available acarcidial and insecticidal formulation to control house dust mites has been completely missing. Therefore the efficacy of 26 formulations of biocides to Deramatophagoides pteronyssinus was compared in the laboratory essay. Among the tested biocides, Acarosan ® duo, Biolit Plus, Allergoff 200 SC and Fedorex-Profi are labeled exclusively against house dust mites. The aim of our work was to find the most effective biocide formulation. The experiments were carried out in the chambers with biocide impr egnated filter paper. The mortality was checked after 24 hours of pesticide exposure. The data were analyzed by probit analyze and doses for 9 9% mortality were fitted. Based on the laboratory essay, the following formulation were found to be satisfactory effective: Acarosan ® duo, Allergoff 200 SC, Biolit Plus, Cascade 5 EC, Crackdown Rapide, Fedorex-Profi, Omite 570 EW, Reslin 25 SE, Sanmite 20 WP and Vertimec 1,8 EC.
Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.
- MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- cisplatina škodlivé účinky MeSH
- dioxoly farmakologie terapeutické užití MeSH
- fytoterapie * MeSH
- ledviny účinky léků metabolismus MeSH
- lignany farmakologie terapeutické užití MeSH
- nemoci ledvin chemicky indukované farmakoterapie metabolismus MeSH
- potkani Wistar MeSH
- preklinické hodnocení léčiv MeSH
- protinádorové látky škodlivé účinky MeSH
- rostlinné extrakty terapeutické užití MeSH
- Sesamum * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH