Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds.

Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.

Human recombinant interleukin-38 suppresses inflammation in mouse models of local and systemic disease.

Interleukin (IL)-38 belongs to the IL-1 family and is part of the IL-36 subfamily due to its binding to the IL-36 Receptor (IL-1R6). In the current study, we assessed the anti-inflammatory properties of IL-38 in murine models of arthritis and systemic inflammation. First, the anti-inflammatory properties of mouse and human IL-38 precursors were compared to forms with a truncated N-terminus. In mouse bone marrow derived dendritic cells (BMDC), human and mouse IL-38 precursors with a truncation of the two N-terminal amino acids (3-152) suppressed LPS-induced IL-6. Recombinant human IL-38 (3-152) was further investigated for its immunomodulatory potential using four murine models of inflammatory disease: streptococcal cell wall (SCW)-induced arthritis, monosodium urate (MSU) crystal-induced arthritis, MSU crystal-induced peritonitis, and systemic endotoxemia. In each of these models IL-38 significantly reduced inflammation. In SCW and MSU crystal-induced arthritis, joint swelling, inflammatory cell influx, and synovial levels of IL-1ß, IL-6, and KC were reduced by 50% or greater. These suppressive properties of IL-38 in SCW-induced arthritis were independent of the anti-inflammatory co-receptor IL-1R8, as IL-38 reduced arthritis equally in IL-1R8 deficient and WT mice. In MSU crystal-induced peritonitis, IL-38 reduced hypothermia, while plasma IL-6 and KC and peritoneal KC levels were reduced by 65-70%. In the LPS endotoxemia model, IL-38 pretreatment reduced systemic IL-6, TNFα and KC. Furthermore, in ex vivo cultured bone marrow, LPS-induced IL-6, TNFα and KC were reduced by 75-90%. Overall, IL-38 exhibits broad anti-inflammatory properties in models of systemic and local inflammation and therefore may be an effective cytokine therapy.

Conditioned Medium of Mesenchymal Stromal Cells: A New Class of Therapeutics.

Mesenchymal stromal cell (MSCs) represent a class of biologics with the prospects for employment as immunomodulatory, tissue-protective, and regenerative therapeutics. In parallel with cellular therapy, cell-free therapy based on MSC-secreted bioactive factors is being actively developed. MSCs secrete a variety of protein, peptide, RNA, and lipid mediators which can be concentrated, frozen, or even lyophilized without loss of activity, which gives them a certain advantage over cellular products requiring liquid nitrogen storage and infrastructure to revive frozen cells. This review (i) describes currently conducted clinical trials of cell-free products containing MSC secretome; (ii) summarizes main approaches to the generation and characterization of conditioned media concentrates and extracellular vesicle isolates; (iii) analyzes a variety of preclinical studies where effectiveness of secretome products has been shown; and (iv) summarizes current knowledge about secretome bioactive components obtained by analysis of in vivo models testing the therapeutic potential of the MSC secretome.

Prophylactic effects of probiotic Bifidobacterium spp. in the resolution of inflammation in arthritic rats.

In the present study, the modulatory effects of bifidobacterial spp. (Bifidobacterium breve NCIM 5671, Bifidobacterium longum NCIM 5672 and Bifidobacterium bifidum NCIM 5697) on adjuvant induced arthritis in rats were evaluated. Arthritis was induced in male Wistar rats by injecting 250 µg of Freund's adjuvant directly into the paw. Fifteen days before and 15 days after the induction of arthritis, suspended cultures of bifidobacteria (109 cfu/ml) were administered by oral gavage. Paw volume, bone mineral content, oxidative stress markers, antioxidant enzymes, cytokines, eicosanoids and expression of COX2, as well as bone hydrolytic enzymes, were assessed by RT PCR. Although piroxicam-treated groups (drug control) had better effects than bifidobacteria-treated groups, bifidobacteria probiotics administration exhibited significant (P < 0.05) prophylactic effects in terms of downregulating arthritis markers. Parameters including paw volume, bone mineral content, cytokines, and eicosanoids level were significantly (p < 0.05) modulated in bifidobacteria administered groups compared to arthritic control group. Among the three strains tested, B. breve NCIM 5671 exhibited superior prophylactic effects as assessed in the experimental rat model of arthritis. In conclusion, bifidobacteria probiotics administration can downregulate the markers of arthritis and hence can be a potential therapeutic regimen in the treatment of arthritis.

[Osteoarticular protection of Zea mays L. purple variety (purple corn) in experimental arthritis in rats]. / Protección osteoarticular de Zea mays L. variedad morada (maíz morado) en artritis experimental en ratas.

OBJECTIVES.: To evaluate the protective effect of Zea mays L., purple variety (purple corn) against inflammatory response and osteoarticular damage in rats with experimental arthritis. MATERIALS AND METHODS.: Sixty-five Holtzman rats were used, assigned to seven groups: G1 (n=5): control; G2 (n=10): pristane (PIA) + distilled water; G3 (n=10): PIA + methotrexate 0.1 mg/kg; G4 (n=10): PIA + indomethacin 0.6 mg/kg; G5 (n=10): PIA + Zea mays 100 mg/kg; G6 (n=10): PIA + Zea mays 1000 mg/kg, and G7 (n=10): PIA + methotrexate 0.1 mg/kg + Zea mays 1000 mg/kg. Treatments were administered by orogastric cannula daily for 21 days; pristane was administered subdermal only on day 1. Volume of hind leg was recorded with a digital plethysmometer. The radiological analysis of the legs was evaluated according to the modified Clark criteria. RESULTS.: The percentage of inflammation at the end of the experiment was: (G1) 1.50 ± 0.5; (G2) 13.73 ± 8.4; (G3) 14.76 ± 8.8; (G4) 14.22 ± 9.0; (G5) 10.81 ± 9.1; (G6) 5.31 ± 1.4; (G7) 6.38 ± 0.5. The radiological scores of the affected areas were: (G1) 0.6; (G2) 3.5; (G3) 0.6; (G4) 1.7; (G5) 1.9; (G6) 1.4; (G7) 1.0. Only the groups Zea mays L. 1000 mg/kg and methotrexate + Zea mays L. 1000 mg/kg showed a significantly lower inflammatory response (p<0.05) and showed significantly lower joint scores in relation to PIA. CONCLUSIONS.: Zea mays L. (purple corn) reduces the inflammatory process and radiological modifications of PIA-induced arthritis in rats in a dose-dependent manner.

OBJETIVOS.: Evaluar el efecto protector de Zea mays L. variedad morada (maíz morado) frente a la respuesta inflamatoria y daño osteoarticular en ratas con artritis experimental. MATERIALES Y MÉTODOS.: Se emplearon 65 ratas Holtzman, asignadas en siete grupos: G1 (n=5): control, G2 (n=10): pristane (PIA) + agua destilada, G3 (n=10): PIA + metotrexate 0,1 mg/kg, G4 (n=10): PIA + indometacina 0,6 mg/kg, G5 (n=10): PIA + Zea mays 100 mg/kg, G6 (n=10): PIA + Zea mays 1000 mg/kg y G7 (n=10): PIA + metotrexate 0,1 mg/kg + Zea mays 1000 mg/kg. Los tratamientos fueron administrados mediante cánula orogástrica diariamente durante 21 días; el pristane se administró vía subdérmica solo el día 1. Se registró el volumen de pata trasera con un pletismometro digital. El análisis radiológico de las patas se evaluó según los criterios de Clark modificado. RESULTADOS.: El porcentaje de inflamación al final del experimento fue: (G1) 1,50 ± 0,5, (G2) 13,73 ± 8,4; (G3) 14,76 ± 8,8; (G4) 14.22 ± 9,0; (G5) 10,81 ± 9.1; (G6) 5,31 ± 1.4; (G7) 6,38 ± 0,5. Los puntajes radiológicos de las áreas afectadas fueron: (G1) 0,6; (G2) 3,5; (G3) 0,6; (G4) 1,7; (G5) 1,9; (G6) 1,4; (G7) 1,0. Solo los grupos Zea mays L. 1000 mg/kg y metotrexate + Zea mays L. 1000 mg/kg mostraron una respuesta inflamatoria significativamente menor (p<0,05) y mostraron puntajes articulares significativamente bajos en relación a PIA. CONCLUSIONES.: El Zea mays L. (maíz morado) reduce el proceso inflamatorio y las modificaciones radiológicas de la artritis inducida por PIA en ratas de modo dosis dependiente.

Protección osteoarticular de Zea mays L. variedad morada (maíz morado) en artritis experimental en ratas / Osteoarticular protection of Zea mays L. purple variety (purple corn) in experimental arthritis in rats

RESUMEN Objetivos. Evaluar el efecto protector de Zea mays L. variedad morada (maíz morado) frente a la respuesta inflamatoria y daño osteoarticular en ratas con artritis experimental. Materiales y métodos. Se emplearon 65 ratas Holtzman, asignadas en siete grupos: G1 (n=5): control, G2 (n=10): pristane (PIA) + agua destilada, G3 (n=10): PIA + metotrexate 0,1 mg/kg, G4 (n=10): PIA + indometacina 0,6 mg/kg, G5 (n=10): PIA + Zea mays 100 mg/kg, G6 (n=10): PIA + Zea mays 1000 mg/kg y G7 (n=10): PIA + metotrexate 0,1 mg/kg + Zea mays 1000 mg/kg. Los tratamientos fueron administrados mediante cánula orogástrica diariamente durante 21 días; el pristane se administró vía subdérmica solo el día 1. Se registró el volumen de pata trasera con un pletismometro digital. El análisis radiológico de las patas se evaluó según los criterios de Clark modificado. Resultados. El porcentaje de inflamación al final del experimento fue: (G1) 1,50 ± 0,5, (G2) 13,73 ± 8,4; (G3) 14,76 ± 8,8; (G4) 14.22 ± 9,0; (G5) 10,81 ± 9.1; (G6) 5,31 ± 1.4; (G7) 6,38 ± 0,5. Los puntajes radiológicos de las áreas afectadas fueron: (G1) 0,6; (G2) 3,5; (G3) 0,6; (G4) 1,7; (G5) 1,9; (G6) 1,4; (G7) 1,0. Solo los grupos Zea mays L. 1000 mg/kg y metotrexate + Zea mays L. 1000 mg/kg mostraron una respuesta inflamatoria significativamente menor (p<0,05) y mostraron puntajes articulares significativamente bajos en relación a PIA. Conclusiones. El Zea mays L. (maíz morado) reduce el proceso inflamatorio y las modificaciones radiológicas de la artritis inducida por PIA en ratas de modo dosis dependiente.

ABSTRACT Objectives. To evaluate the protective effect of Zea mays L., purple variety (purple corn) against inflammatory response and osteoarticular damage in rats with experimental arthritis. Materials and Methods. Sixty-five Holtzman rats were used, assigned to seven groups: G1 (n=5): control; G2 (n=10): pristane (PIA) + distilled water; G3 (n=10): PIA + methotrexate 0.1 mg/kg; G4 (n=10): PIA + indomethacin 0.6 mg/kg; G5 (n=10): PIA + Zea mays 100 mg/kg; G6 (n=10): PIA + Zea mays 1000 mg/kg, and G7 (n=10): PIA + methotrexate 0.1 mg/kg + Zea mays 1000 mg/kg. Treatments were administered by orogastric cannula daily for 21 days; pristane was administered subdermal only on day 1. Volume of hind leg was recorded with a digital plethysmometer. The radiological analysis of the legs was evaluated according to the modified Clark criteria. Results. The percentage of inflammation at the end of the experiment was: (G1) 1.50 ± 0.5; (G2) 13.73 ± 8.4; (G3) 14.76 ± 8.8; (G4) 14.22 ± 9.0; (G5) 10.81 ± 9.1; (G6) 5.31 ± 1.4; (G7) 6.38 ± 0.5. The radiological scores of the affected areas were: (G1) 0.6; (G2) 3.5; (G3) 0.6; (G4) 1.7; (G5) 1.9; (G6) 1.4; (G7) 1.0. Only the groups Zea mays L. 1000 mg/kg and methotrexate + Zea mays L. 1000 mg/kg showed a significantly lower inflammatory response (p<0.05) and showed significantly lower joint scores in relation to PIA. Conclusions. Zea mays L. (purple corn) reduces the inflammatory process and radiological modifications of PIA-induced arthritis in rats in a dose-dependent manner.

Comparative immunosecretome analysis of prevalent Streptococcus suis serotypes.

Streptococcus suis is a major Gram-positive swine pathogen associated with a wide variety of diseases in pigs. The efforts made to develop vaccines against this pathogen have failed because of lack of common cross-reactive antigens against different serotypes. Nowadays the interest has moved to surface and secreted proteins, as they have the highest chances to raise an effective immune response because they are in direct contact with host cells and are really exposed and accessible to antibodies. In this work, we have performed a comparative immunosecretomic approach to identify a set of immunoreactive secreted proteins common to the most prevalent serotypes of S. suis. Among the 67 proteins identified, three (SSU0020, SSU0934, and SSU0215) were those predicted extracellular proteins most widely found within the studied serotypes. These immunoreactive proteins may be interesting targets for future vaccine development as they could provide possible cross-reactivity among different serotypes of this pathogen.

Anti-inflammatory and anti-arthritic effects of methanol extract of the stem bark of Boswellia dalzielii Hutch (Burseraceae) in rats.

Boswellia dalzielii is a tall tree (more than 13 m high) that produces aromatic white flowers. This plant is commonly used in indigenous medicine across Africa against diarrhea, malaria, vomiting, inflammation and arthritis. The present study focuses on the anti-inflammatory and anti-arthritis potential of methanol extract of Boswellia dalzielii (BDME). Anti-inflammatory activity was evaluated in inflammatory models induced by carrageenan, arachidonic acid, histamine, serotonin, prostaglandin and bradykinin. Anti-arthritis activity was measured using complete Freund's adjuvant model. Intracellular and extracellular ROS production and proliferation of T-cells were evaluated using chemiluminescence and liquid scintillation counter techniques, respectively. TNF-α and IL-1ß production were assessed using ELISA and MTT assay performed for cytotoxicity. BDME revealed a significant anti-inflammatory effect by preventing the development of edema caused by carrageenan, arachidonic acid, histamine, serotonin, prostaglandin and bradykinin. For anti-arthritic properties of BDME, the results showed a significant reduction of the joint diameter and a decrease in pain in the treated animals. The extract also showed a noticeable systemic effect, maintaining the values of the evaluated parameters close to normal in treated rats with an inhibition of joint destruction as shown in histopathological analysis. Furthermore, BDME exhibited significant inhibition of extracellular and intracellular ROS production. Still, the extract displayed significant inhibitory activity on T-cell proliferation as well as a reduced production of TNF-α and IL-1ß. Boswellia dalzielii could be considered as a promising tract in the prevention and/or management of inflammatory diseases.

The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update.

The concept of using phytochemicals has ushered in a new revolution in pharmaceuticals. Naturally occurring polyphenols (like curcumin, morin, resveratrol, etc.) have gained importance because of their minimal side effects, low cost and abundance. Curcumin (diferuloylmethane) is a component of turmeric isolated from the rhizome of Curcuma longa. Research for more than two decades has revealed the pleiotropic nature of the biological effects of this molecule. More than 7000 published articles have shed light on the various aspects of curcumin including its antioxidant, hypoglycemic, anti-inflammatory and anti-cancer activities. Apart from these well-known activities, this natural polyphenolic compound also exerts its beneficial effects by modulating different signalling molecules including transcription factors, chemokines, cytokines, tumour suppressor genes, adhesion molecules, microRNAs, etc. Oxidative stress and inflammation play a pivotal role in various diseases like diabetes, cancer, arthritis, Alzheimer's disease and cardiovascular diseases. Curcumin, therefore, could be a therapeutic option for the treatment of these diseases, provided limitations in its oral bioavailability can be overcome. The current review provides an updated overview of the metabolism and mechanism of action of curcumin in various organ pathophysiologies. The review also discusses the potential for multifunctional therapeutic application of curcumin and its recent progress in clinical biology.

Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.

INTRODUCTION: Interleukin (IL)-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines. METHODS: To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays. RESULTS: Diseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays. CONCLUSION: Thus we conclude that IL-36α does not affect the development of inflammatory arthritis.

The effect of antimicrobial treatment and preventive strategies on bovine respiratory disease and genetic relatedness and antimicrobial resistance of Mycoplasma bovis isolates in a western Canadian feedlot.

Feedlot calves (n = 3784) were systematically randomized and allocated in a 2 × 2 factorial study to receive metaphylactic oxytetracycline (OTC) on arrival or no antimicrobial, as well as florfenicol once subcutaneously or twice intramuscularly (48 h apart) if diagnosed with bovine respiratory disease (BRD). Calves of different treatment groups were comingled and followed from placement to re-implantation (~100 days). Animals receiving OTC had a reduced risk of BRD, an increased risk of arthritis, and no significant differences in average daily gain, BRD relapse, overall mortality, or BRD mortality. There were no significant differences between treatment protocols. Deep nasal swabs (n = 233) taken at arrival (n = 122), treatment (n = 77), and swabs from lungs and joints at postmortem (n = 34) were cultured for Mycoplasma bovis from 61 animals ill or dying of chronic pneumonia and arthritis and from 61 healthy calves. There was significant variation in diversity among isolates (n = 51) between study years and different cattle. Metaphylaxis or antimicrobial treatment did not affect the diversity of isolates. Except for tilmicosin, isolates were largely susceptible to tested antimicrobials.

Effet du traitement antimicrobien et des stratégies préventives sur le complexe respiratoire bovin ainsi que la relation génétique et l'antibiorésistance des isolats deMycoplasma bovisdans un parc d'engraissement de l'Ouest canadien. Les veaux d'un parc d'engraissement (n = 3784) ont été systématiquement randomisés et répartis dans une étude factorielle 2 × 2 pour recevoir de l'oxytétracycline métaphylactique (OTC) à l'arrivée ou pas d'antimicrobien, ainsi qu'une injection sous-cutanée ou deux injections intramusculaires (à intervalle de 48 h) de florfénicol s'ils étaient diagnostiqués avec le complexe respiratoire bovin (CRB). Les veaux de différents groupes de traitement ont été regroupés pêle-mêle et suivis du placement à la réimplantation (~100 jours). Les animaux recevant l'OTC avaient un risque réduit de CRB, un risque accru d'arthrite et ne présentaient pas de différences significatives pour le gain de poids quotidien moyen, la rechute du CRB, la mortalité globale ou la mortalité associée au CRB. Il n'y avait aucune différence significative entre les protocoles de traitement. Des écouvillonnages nasaux profonds (n = 233) prélevés à l'arrivée (n = 122), au traitement (n = 77) et des écouvillonnages des poumons et des articulations post mortem (n = 34) ont été cultivés pour Mycoplasma bovis à partir de 61 animaux malades ou mourants de pneumonie chronique et d'arthrite et de 61 veaux en santé. Il n'y avait aucune variation significative dans la diversité des isolats (n = 51) entre les années d'étude et les différents bovins. La métaphylaxie ou le traitement antimicrobien n'a pas affecté la diversité des isolats. Sauf pour la tilmicosine, les isolats étaient largement sensibles aux antimicrobiens testés.(Traduit par Isabelle Vallières).

Grape seed proanthocyanidin extract-mediated regulation of STAT3 proteins contributes to Treg differentiation and attenuates inflammation in a murine model of obesity-associated arthritis.

Grape seed proanthocyanidin extract (GSPE) is a natural flavonoid that exerts anti-inflammatory properties. Obesity is an inflammatory condition and inflammatory cells and their secretion of pro-inflammatory molecules contribute to the pathogenesis of obesity. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by inflammation of joints lined by synovium. Previously, we demonstrated that obesity augmented arthritis severity in collagen induced arthritis (CIA), a murine model of human RA. Here, we investigated whether oral administration of GSPE showed antiobesity and anti-arthritic effects in high-fat diet-induced obese (DIO) mice and in obese CIA mice, respectively. The pathophysiologic mechanisms by which GSPE attenuates weight gain and arthritis severity in vivo were also investigated. In DIO mice, GSPE administration significantly inhibited weight gain, reduced fat infiltration in liver and improved serum lipid profiles. The antiobesity effect of GSPE was associated with increased populations of regulatory T (Treg) cells and those of decreased Th17 cells. Decrease of Th17 cells was associated with significant inhibition of their key transcriptional factors, pSTAT3(Tyr705) and pSTAT3(Ser727). On the contrary, GSPE-induced Treg induction was associated with enhanced pSTAT5 expression. To identify the anti-arthritis effects of GSPE, GSPE was given orally for 7 weeks after type II collagen immunization. GSPE treatment significantly attenuated the development of autoimmune arthritis in obese CIA model. In line with DIO mice, GSPE administration decreased Th17 cells and reciprocally increased Treg cells by regulating STAT proteins in autoimmune arthritis model. The expressions of pro-inflammatory cytokines and nitrotyrosine in synovium were significantly inhibited by GSPE treatment. Taken together, GSPE functions as a reciprocal regulator of T cell differentiation - suppression of Th17 cells and induction of Tregs in both DIO and obese CIA mice. GSPE may act as a therapeutic agent to treat immunologic diseases related with enhanced STAT3 activity such as metabolic disorders and autoimmune diseases.

Exploration of functional food consumption in older adults in relation to food matrices, bioactive ingredients, and health.

The functional food industry is expanding, yet research into consumer perceptions of functional foods is limited. Older adults could benefit from functional foods due to age-related food and health issues. This research gathered information about functional foods from community-dwelling older adults (n = 200) who completed a researcher-administered questionnaire about consumption, food matrices, bioactive ingredients, and health areas addressed through functional foods. Overall prevalence of functional food consumption was found to be 93.0%. Commonly consumed foods included yogurt with probiotics (56.0%), eggs with omega-3 fatty acids (37.0%), and bread with fiber (35.5%). Functional food matrices primarily consumed were yogurt (51.5%), bread (44.0%), and cereal (40.0%). The primary functional food bioactive consumed was dietary fiber (79.5%). Most participants (86.2%) indicated that they consume functional foods to improve health, and the major areas specified were osteoporosis/bone health (67.5%), heart disease (61.0%), and arthritis (55.0%). These results inform health professionals regarding the potential of functional foods to support health among older adults.

Transdermal microemulsion drug delivery system for impairing male reproductive toxicity and enhancing efficacy of Tripterygium Wilfordii Hook f.

The present study is trying to produce a transdermal microemulsion drug delivery system (TMDDS) for Tripterygium Wilfordii Hook f. (TWHF) and attempting to solve male reproductive toxicity problem of TWHF. The formulation was optimized by the central composite design with response surface methodology and was decided as 12% oleic acid, 19.7% Labrasol S, 19.7% ethanol and 19.7% Pharmasolve, and 29% water. TMDDS for TWHF had stronger transdermal ability than free TWHF, and TWHF microemulsion significantly inhibited the adjuvant-induced arthritis and at the same time, had preferable anti-inflammatory effect with the long-time administration. Various pharmacodynamics parameters proved that TWHF microemulsion can reduce the male reproductive toxicity and hepatotoxicity of rats. All these suggested that TMDDS could be a suitable delivery system for TWHF.

Antioxidant content and activity of the Indian fresh-water pearl mussel in the prevention of arthritis in an experimental animal model.

The flesh of the Indian fresh-water mussel, Lamellidens marginalis (LM; Lamarck, 1819), is the byproduct of pearl culture and a cheap protein source. The present study investigated the antioxidant content of this ethnomedicinally cited species to outline its importance in food security and disease prevention. LM was found to be rich in polyphenol antioxidants with good correlation with its reducing capacity. LM also showed a significant free-radical-scavenging activity, H(2)O(2)-scavenging activity and Fe-chelating activity. To study the effect of this dietary antioxidant against oxidative stress, we took inflammatory arthritis as a model. LM-treated arthritis rats showed a higher antioxidant defence system with elevated superoxide dismutase, total thiol, glutathione S transferase, glutathione peroxidase, total antioxidant status and catalase concentration of haemolysate. Oxidative stress markers like serum thiobarbituric acid-reacting substances, methyl glyoxal, NO and total oxidant status levels were decreased in LM-treated arthritis rats. Hence, the dietary antioxidants of LM were found to be effective in the prevention of oxidative stress in inflammatory arthritis. In conclusion, LM, the cash-crop byproduct, provides a rare opportunity for income and nutrition, not only by providing cheap and available energy, protein and dietary factors, but also by providing antioxidants effective against chronic inflammatory disease.

Pathophysiology and pharmacologic control of osseous mandibular condylar resorption.

PURPOSE: When osseous mandibular condylar resorption occurs there can be many different diagnoses: inflammatory arthritis, TMJ compression, trauma, hormone imbalances, and others. While each diagnosis has its own original inciting event, the pathophysiological pathway for articular bone loss is the same. The aim of this article is to review the relevant literature on condylar resorption and the use of pharmacotherapy to control arthritic erosions and resorption. MATERIALS AND METHODS: The literature search was performed using PubMed database with various combinations of related keywords. Preference was given to clinical trials when reviewing articles. RESULTS: The literature reveals that common cellular level events associated with articular resorption include the activation of osteoblasts by cytokines, free radicals, hormone imbalances and/or potent phospholipid catabolites. The osteoblast then activates the recruitment of osteoclasts and promotes the release of matrix degrading enzymes from the osteoclast. Research into articular erosions has focused on elucidating the important steps in the bone destructive pathways and interfering with them by pharmacological means. The use of antioxidants, tetracyclines, omega-3 fatty acids, non-steroidal anti-inflammatories and inflammatory cytokine inhibitors to aid in preventing and controlling articular bone loss including osseous mandibular condylar resorption has been successful. CONCLUSION: By understanding the known pathways that lead to condylar resorption and the individual patient's susceptibilities, targeted pharmacotherapy might be able to disturb these pathways and prevent further condylar resorption. Basic clinical investigations and randomized clinical trials are still required, but the present science is encouraging.

Protective targeting of high mobility group box chromosomal protein 1 in a spontaneous arthritis model.

OBJECTIVE: High mobility group box chromosomal protein 1 (HMGB-1) is a DNA binding nuclear protein that can be released from dying cells and activated myeloid cells. Extracellularly, HMGB-1 promotes inflammation. Clinical and experimental studies demonstrate that HMGB-1 is a pathogenic factor in chronic arthritis. Mice with combined gene deficiency for DNase II and IFNRI spontaneously develop chronic, destructive polyarthritis with many features shared with rheumatoid arthritis. DNase II is needed for macrophage degradation of engulfed DNA. The aim of this study was to evaluate a potential pathogenic role of HMGB-1 in this novel murine model. METHODS: The course of arthritis, assessed by clinical scoring and histology, was studied in DNase II(-/-) × IFNRI(-/-) mice, in comparison with heterozygous and wild-type mice. Synovial HMGB-1 expression was analyzed by immunohistochemistry. Serum levels of HMGB-1 were determined by Western immunoblotting and enzyme-linked immunosorbent assay (ELISA), and anti-HMGB-1 autoantibodies were detected by ELISA. Macrophage activation was studied by immunostaining for intracellular interleukin-1ß and HMGB-1. HMGB-1 was targeted with truncated HMGB-1-derived BoxA protein, acting as a competitive antagonist, with intraperitoneal injections every second day for 5 weeks. RESULTS: DNase II(-/-) × IFNRI(-/-) mice developed symmetric polyarthritis with strong aberrant cytosolic and extracellular HMGB-1 expression in synovial tissue, in contrast to that observed in control animals. Increased serum levels of HMGB-1 and HMGB-1 autoantibodies were recorded in DNase II(-/-) × IFNRI(-/-) mice, both prior to and during the establishment of disease. Systemic HMGB-1-specific blockade significantly ameliorated the clinical disease course, and a protective effect on joint destruction was demonstrated by histologic evaluation. CONCLUSION: HMGB-1 is involved in the pathogenesis of this spontaneous polyarthritis, and intervention with an HMGB-1 antagonist can mediate beneficial effects.

Transgenic disruption of glucocorticoid signaling in mature osteoblasts and osteocytes attenuates K/BxN mouse serum-induced arthritis in vivo.

OBJECTIVE: Endogenous glucocorticoids (GCs) modulate numerous biologic systems involved in the initiation and maintenance of arthritis. Bone cells play a critical role in the progression of arthritis, and some of the effects of GCs on inflammation may be mediated via these cells. The aim of this study was to investigate the impact of osteoblast-targeted disruption of GC signaling on joint inflammation, cartilage damage, and bone metabolism in the K/BxN mouse serum transfer model of autoimmune arthritis. METHODS: Intracellular GC signaling was disrupted in osteoblasts through transgenic overexpression of 11beta-hydroxysteroid dehydrogenase type 2 under the control of a type I collagen promoter. Arthritis was induced in 5-week-old male transgenic mice and their wild-type (WT) littermates, and paw swelling was assessed daily until the mice were killed. The mice were examined by histology, histomorphometry, and microfocal computed tomography, and serum was analyzed for cytokines, adrenocorticotropic hormone, and corticosterone. RESULTS: Acute arthritis developed in both transgenic and WT mice treated with K/BxN mouse serum. However, the arthritis and local inflammatory activity were significantly attenuated in transgenic mice, as judged by clinical and histologic indices of inflammation and cartilage damage. Bone turnover and bone volume remained unchanged in arthritic transgenic mice, while WT mice exhibited stimulated bone resorption, suppressed osteoblast activity, and significantly reduced bone volume, compatible with the known effects of active inflammation on bone. Circulating levels of proinflammatory cytokines tended to be lower in arthritic transgenic mice than in control transgenic mice. CONCLUSION: Disruption of GC signaling in osteoblasts significantly attenuates K/BxN mouse serum-induced autoimmune arthritis in mice. These data suggest that osteoblasts modulate the immune-mediated inflammatory response via a GC-dependent pathway.