Management of Osteoarthritis with Avocado/Soybean Unsaponifiables.

Osteoarthritis (OA) is a painful and life-altering disease that severely limits the daily activity of millions of Americans, and is one of the most common causes of disability in the world. With obesity on the rise and the worlds population living longer, the prevalence of OA is expected to increase dramatically in the coming decades, generating burdensome socioeconomic costs. This review summarizes current pharmaceutical, non-pharmaceutical, and prospective new treatments for OA, with primary focus on the dietary supplement Avocado/Soybean Unsaponifiables (ASU). ASU modulates OA pathogenesis by inhibiting a number of molecules and pathways implicated in OA. Anticatabolic properties prevent cartilage degradation by inhibiting the release and activity of matrix metalloproteinases (MMP-2,3,13) and increasing tissue inhibitors of these catabolic enzymes (TIMP-1). ASU also inhibits fibrinolysis by stimulating the expression of plasminogen activator inhibitor (PAI-1). Anabolic properties promote cartilage repair by stimulating collagen and aggrecan synthesis via inhibition of inflammatory cytokines such as IL1, IL6, IL8, TNF, ERK, and PGE2. Chondroprotective effects are mediated by correcting growth factor abnormalities, increasing TGFβ while decreasing vascular endothelial growth factor (VEGF) in synovial fluid. ASU also inhibits cholesterol absorption and endogenous cholesterol biosynthesis, which mediate reactive oxygen species pathology in chondrocytes. At the clinical level, ASU reduces pain and stiffness while improving joint function, resulting in decreased dependence on analgesics

Evaluating the comparative effects of Listerine zero and Persica mouthwashes on the periodontal conditions of fixed orthodontics patients

Background and Objective: Periodontal problems are very common among patients undergoing fixed orthodontics treatment. Using mouthwashes such as Listerine and Persica is recommended in order to prevent such complications. There have, however, been no information on the comparative effects of Listerine and Persica mouthwashes so far. Thus the comparative study presented here under the title of “Evaluating the comparative effects of Listerine Zero and Persica Mouthwashes on the Periodontal Conditions of fixed orthodontics Patients was conducted at the Department of Dentistry of Azad University of Tehran. Materials and Methods: A blind randomized clinical trial was conducted on 30 patients. All subjects were between 20 and 50 years of age; had been under fixed orthodontic treatment for at least two months; did not have serious systemic health complications; had a minimum of 5 teeth in each quadrant for evaluation. Root planning and scaling were conducted on male and female subjects prior to their entry into the study. The SI, GI, PI, and BOP indices of each subject were then recorded in the base-line stage. The subjects were then divided into two random groups. The first group was treated with Persica (Pursina Co., Iran) and the second group with Listerine Zero (Johnson & Johnson, New Jersey, USA). The two groups were followed up twice after two and four weeks of treatment and their SI, GI, PI, and BOP indices were recorded. Results: The SI, GI, PI, and BOP indices were found to have changed by similar amounts in both groups (P<0.12). The changes in GI, PI, and BOP were, however, statistically significant within each group (P<0.02). The changes in SI index within the Persica group were found to increase only within the first two weeks of treatment (P<0.05). Conclusion: Following the comparative study described above, both mouthwashes appear to positively affect the periodontal condition of fixed orthodontics patients. Both mouthwashes were, however, found to have similar effects

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

ROLE FONCTIONNEL DES PROTEINES G HETEROTRIMERIQUES G(ALPHA)OLF, G(ALPHA)O/I ET G BETA-GAMMA DANS LE SYSTEME ENDOCRINE BETA-PANCREATIQUE, L'EPITHELIUM DIGESTIF ET UROGENITAL

LES PROTEINES G HETEROTRIMERIQUES JOUENT UN ROLE CLE DANS LA TRANSDUCTION DES SIGNAUX EXTRACELLULAIRES ET SONT IMPLIQUEES DANS DE NOMBREUX PROCESSUS PHYSIOPATHOLOGIQUES COMME LA SECRETION D'INSULINE ET LA TRANSFORMATION CELLULAIRE, NOTAMMENT GS. NOUS AVONS CONSIDERE, ICI, LE ROLE FONCTIONNEL DE SON HOMOLOGUE GOLF, INITIALEMENT CARACTERISEE DANS L'EPITHELIUM ET LE BULBE OLFACTIFS, PUIS DANS LE PANCREAS ENDOCRINE ET LE SYSTEME DIGESTIF ET UROGENITAL. NOUS AVONS DEMONTRE QUE LA PROTEINE GOLF EST EXPRIMEE DANS LES CELLULES -PANCREATIQUES SECRETRICES D'INSULINE ET QU'ELLE STIMULE PREFERENTIELLEMENT LES ADENYLATES CYCLASES I ET VIII. D'AUTRE PART, LA SUREXPRESSION DE SA FORME CONSTITUTIVEMENT ACTIVEE, AGOLF, OU SAUVAGE, WTGOLF EST ASSOCIEE A LA DESENSIBILISATION DE LA SECRETION DE L'INSULINE ET A LA DEPLETION DE SON STOCKAGE DANS LES CELLULES PANCREATIQUES TC3. ENFIN, LA SUREXPRESSION DE AGOLF INHIBE L'APOPTOSE DE CES CELLULES SOUMISES A LA PRIVATION DE SERUM. NOUS AVONS EGALEMENT MONTRE QUE AGOLF INDUISAIT L'INVASION CELLULAIRE DANS TROIS MODELES REPRESENTATIFS DU TRACTUS DIGESTIF ET UROGENITAL, LES CELLULES EPITHELIALES RENALES MDCKTS.SRC, COLORECTALES HCT-8/S11 ET PROSTATIQUES LNCAP. L'INVASION INDUITE PAR AGOLF EST DEPENDANTE DE LA PI3K, DES GTPASES RHO ET DE LA PKC, MAIS INDEPENDANTE DE LA PKA ET DE LA PLC. ALORS QUE AGOLF INDUIT LA SURVIE DES CELLULES MDCKTS.SRC CULTIVEES EN ABSENCE DE SERUM, PAR UN MECANISME INDEPENDANT DE RHO, CETTE PROTEINE G ENTRAINE LA DIFFERENCIATION NEURO-ENDOCRINE DANS LES CELLULES LNCAP, SELON DES VOIES DEPENDANTES DE LA PKA ET DE RHO. CETTE DIFFERENCIATION SE TRADUIT PAR L'INDUCTION DU PEPTIDE PTHRP, IMPLIQUE DANS LA PROGRESSION NEOPLASIQUE. ENFIN, NOUS AVONS DEMONTRE QUE LE RECEPTEUR DU PAF INHIBE L'INVASION CELLULAIRE INDUITE PAR SRC, MET ET LA LEPTINE, EN EMPRUNTANT LES PROTEINES G PTX-SENSIBLES, GO, GIL, 2 ET 3. EN REVANCHE, LE COMPLEXE G LIBERE SUITE A L'ACTIVATION DES PROTEINES GO/I EST UN MEDIATEUR CRITIQUE DES VOIES DE SIGNALISATION PRO-INVASIVES. IL EXISTE DONC UN ANTAGONISME LATENT ENTRE CES GO/I ET G, EN FAVEUR DE LA SIGNALISATION NEGATIVE DOMINANTE DANS NOTRE SYSTEME D'INVASION DU COLLAGENE DE TYPE I. L'ENSEMBLE DE CES RESULTATS NOUS PERMET DONC D'ENVISAGER UN ROLE POTENTIEL DE GOLF DANS DEUX PATHOLOGIES DIGESTIVES, LE DIABETE ET LE CANCER.PARIS5-BU Saints-Pères (751062109) / SudocSudocFranceF

Management of Osteoarthritis with Avocado/Soybean Unsaponifiables.

Osteoarthritis (OA) is a painful and life-altering disease that severely limits the daily activity of millions of Americans, and is one of the most common causes of disability in the world. With obesity on the rise and the worlds population living longer, the prevalence of OA is expected to increase dramatically in the coming decades, generating burdensome socioeconomic costs. This review summarizes current pharmaceutical, non-pharmaceutical, and prospective new treatments for OA, with primary focus on the dietary supplement Avocado/Soybean Unsaponifiables (ASU). ASU modulates OA pathogenesis by inhibiting a number of molecules and pathways implicated in OA. Anticatabolic properties prevent cartilage degradation by inhibiting the release and activity of matrix metalloproteinases (MMP-2,3,13) and increasing tissue inhibitors of these catabolic enzymes (TIMP-1). ASU also inhibits fibrinolysis by stimulating the expression of plasminogen activator inhibitor (PAI-1). Anabolic properties promote cartilage repair by stimulating collagen and aggrecan synthesis via inhibition of inflammatory cytokines such as IL1, IL6, IL8, TNF, ERK, and PGE2. Chondroprotective effects are mediated by correcting growth factor abnormalities, increasing TGFβ while decreasing vascular endothelial growth factor (VEGF) in synovial fluid. ASU also inhibits cholesterol absorption and endogenous cholesterol biosynthesis, which mediate reactive oxygen species pathology in chondrocytes. At the clinical level, ASU reduces pain and stiffness while improving joint function, resulting in decreased dependence on analgesics

Eotaxin-3/CCL26 gene expression in intestinal epithelial cells is up-regulated by interleukin-4 and interleukin-13 via the signal transducer and activator of transcription 6

Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at sites of inflammation. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. Eotaxin-3/CCL-26 belongs to a family of CC chemokines, which are potent chemoattractants for eosinophils. In this study, we hypothesized that intestinal epithelial cells could release eotaxin-3. We demonstrate that the T helper 2 type cytokines interleukin-4 or interleukin-13 increase eotaxin-3 mRNA levels and eotaxin-3 protein expression in the human intestinal epithelial cell lines HT-29 CL.19A and T84 in a dose-dependent manner. Addition of actinomycin-D prior to interleukin-4/-13 stimulation led to decreases in eotaxin-3 mRNA levels similar to those observed in controls without interleukin-4/-13. Interleukin-4 and interleukin-13 activated signal transducer and activator of transcription 6 which was found to bind the two canonical signal transducer and activator of transcription 6 binding sites located in the eotaxin-3 promoter. Experiments with the eotaxin-3 promoter luciferase constructs revealed that the most proximal signal transducer and activator of transcription 6 binding site located between positions -62 and -71 relative to the transcriptional start was necessary for full eotaxin-3 promoter activity. Importantly, we present evidence that the signal transducer and activator of transcription 6 is necessary and sufficient for interleukin-4 or interleukin-13 mediated eotaxin-3 gene up-regulation using HT-29 CL.19A cells expressing a dominant-negative signal transducer and activator of transcription 6. Overall, these results demonstrate that epithelial eotaxin-3 is up-regulated in the context of a T helper 2 mediated inflammatory bowel disease via the signal transducer and activator of transcription 6, thus suggesting that the intestinal epithelium actively participates in the recruitment of eosinophils at the site of inflammation