Physical activity as a proxy to ameliorate inflammation in patients with type 2 diabetes and periodontal disease at high cardiovascular risk

While the beneficial impact of physical activity has been ascertained in a variety of pathological scenarios, including diabetes and low-grade systemic inflammation, its potential remains still putative for periodontal health. Periodontal disease has been associated with inflammatory systemic alterations, which share a common denominator with type 2 diabetes mellitus and cardiovascular disease. Physical exercise, along with nutritional counseling, is a cornerstone in the treatment and prevention of type 2 diabetes, also able to reduce the prevalence of periodontal disease and cardiovascular risk. In addition, considering the higher incidence of periodontitis in patients with type 2 diabetes compared to healthy controls, the fascinating research question would be whether physical activity could relieve the inflammatory pressure exerted by the combination of these two diseases. This multi-disciplinary viewpoint discusses available literature in order to argument the hypothesis of a “three–way relationship” linking diabetes, periodontitis, and physical activity.     

Etanercept for refractory asthma therapy

Asthma is a chronic disease of the airways in which inflammation causes bronchial hyper-reactivity and consequent asthma attacks triggered by various stimuli. The bronchospasm attacks are usually relieved by short-acting β₂ agonists, and inflammation and bronchial hyper-reactivity are reduced by maintenance therapy and, in particular, by inhaled corticosteroids. In milder asthma subjects, airway inflammation is dominated by eosinophils, whereas in more severe asthma increased neutrophil counts were detected. In severe/refractory asthma, TNF-α is known to play a role in the maintenance of neutrophilic inflammation and of bronchial hyper-responsiveness and is not influenced by corticosteroid therapy. Etanercept, a TNF-α-blocking agent, could represent one of the potential therapies for refractory asthma based on demonstrated safety and efficacy.     

Identification of biomarkers for essential hypertension based on metabolomics

AimEssential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases.Data synthesisThis review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0.Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development.ConclusionsThis study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.     

Roles of transforming growth factor-α in mammary development and disease

Transforming growth factor-alpha (TGFα) is a member of the epidermal growth factor (EGF) family. Expression of TGFα is highly regulated in response to exogenous cellular signals including cytokines and other growth factors. The growth factor has been found to be indispensable for proper development of many tissues and organs. TGFα has also been implicated in numerous disease states including forms of breast cancer. This minireview summarizes the basic biology of TGFα and its actions during normal and pathogenic development of the mammary epithelium.     

不同时机给药对原发性痛经模型小鼠雌激素受体、缩宫素受体的影响

目的观察不同时机给药对原发性痛经模型小鼠雌激素受体(ER-α)和缩宫素受体(OTR)的影响。方法将km小鼠按体重分层随机分为:JQF动情周期给药组、JQF第4天给药组(JQF剂量均为0.218 g/kg)、元胡止痛片组(0.1 g/kg)、模型组和正常组。除正常组外每日皮下注射苯甲酸雌二醇0.2 mg/只,连续6 d。采用Western blot和Real-time PCR分别检测1周期给药和3周期连续给药对ER-α和OTR蛋白与m RNA表达的影响。结果与模型组比较,JQF动情周期给药组与第4天给药组ER-α和OTR蛋白、m RNA的表达均呈现显著下调(P<0.01)。动情周期给药组和第4天给药组组间比较无差异,3周期连续给药实验结果与1周期一致。结论不同时机给药对原发性痛经模型小鼠ER-α和OTR蛋白、m RNA表达有相同的抑制作用。     

Identification of CD56dim subpopulation marked with high expression of GZMB/PRF1/PI-9 in CD56+ interferon-α-induced dendritic cells

As the sentinels of innate and adaptive immune system, dendritic cells (DCs) have been considered to hold a great promise for medical application. Among the diverse types of DCs, monocyte-derived DCs (mo-DCs) generated in vitro have been most commonly employed. We have been improving the culture protocol and devised a protocol to produce mature interferon-α-induced DCs (IFN-DCs), hereinafter called (mat)IFN-DCs. While exploring the relationship between the expression of CD56 and the cytotoxic activity of (mat)IFN-DCs, we unexpectedly found that sorting of (mat)IFN-DCs with CD56 antibody-coated microbeads (MB) resulted in fractionating cells with tumoricidal activity into the flow-through (FT) but not MB-bound fraction. We uncovered that the FT fraction contains cells expressing low but substantial level of CD56. Moreover, those cells express granzyme B (GrB), perforin (PFN), and serpin B9 at high levels. By employing a specific inhibitor of PFN, we confirmed that direct tumoricidal activity relies on the GrB/PFN pathway. We designated subpopulation in FT fraction as CD56^dim and that in CD56 positively sorted fraction as CD56^bright, respectively. This is the first time, to our knowledge, to identify subpopulations of CD56-positive IFN-DCs with distinct tumoricidal activity which is ascribed to high expression of the components of GrB/PFN pathway.     

Autoantibody production in patients treated with anti-TNF-α

Patients with rheumatoid arthritis, Crohn’s disease or spondyloarthritis who are treated with selective TNF-α inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-dsDNA antibodies. Various methods have shown that infliximab led to ANAs in 29–76.7% and anti-dsDNA antibodies in 10–29% of rheumatoid arthritis patients participating in clinical trials. Furthermore, ANAs and anti-dsDNA antibodies have appeared in 11–36 and 5–15% of rheumatoid arthritis patients treated with etanercept and 12.9% and 5.3% of those treated with adalimumab, respectively. Antiphospholipid antibodies, which are mainly detected by means of anticardiolipin assays, have also been found in rheumatoid arthritis patients receiving TNF-α blockers. There have been a number of reports of the development of antidrug antibodies, of which those against infliximab lead to infusion reactions and shorter responses to treatment. This has led some authors to conclude that it is necessary to add methotrexate to infliximab in order to reduce the risk of the appearance of anti-idiotype autoantibodies     

Contribution of momilactones A and B to diabetes inhibitory potential of rice bran: Evidence from in vitro assays

This study was the first to detect the presence of the two compounds momilactone A (MA) and momilactone B (MB) in rice bran using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). By in vitro assays, both MA and MB exhibited potent inhibitory activities on pancreatic α-amylase and α-glucosidase which were significantly higher than γ-oryzanol, a well-known diabetes inhibitor. Remarkably, MA and MB indicated an effective inhibition on trypsin with the IC₅₀ values of 921.55 and 884.03 µg/mL, respectively. By high-performance liquid chromatography (HPLC), quantities of MA (6.65 µg/g dry weight) and MB (6.24 µg/g dry weight) in rice bran were determined. Findings of this study revealed the α-amylase, α-glucosidase and trypsin inhibitors MA and MB contributed an active role to the diabetes inhibitory potential of rice bran.     

Relationships between blood pressure,anthropometric characteristics and blood lipids in high- and low-altitude populations from Central Asia

We studied the relationships between blood pressure, anthropometric characteristics and blood lipids in 72 low altitude (LA) Uighurs (600m), 91 LA-Kirghizs (900 m), 117 medium altitude (MA) Kazakhs (2100m) and 94 high altitude (HA) Kirghizs (3200 m). All subjects were male and had a similar age (p = ns, ANOVA; range for all 374 subjects: 18-66 yr). Body weight (Wt), body mass index (BMI) and the sum of four skinfolds (4SF) were significantly lower in HA-Kirghizs than the remaining groups (p &lt; 0:0005, p &lt; 0:0005 and p &lt; 0:05 respectively, ANOVA). However, no difference was found in body fat distribution as detected by waist: hip circumference (WHR) and triceps : subscapular skinfold ratios (TSR; p = ns, ANOVA). Stage 1 hypertension was detected in 18% of LA-Uighurs, 2% of LA-Kirghizs, 4% of MA-Kazakhs and 1% of HA-Kirghizs; stage 2 hypertension was detected in 2% of LA-Uighurs and none of the remaining groups; no subject had stage 3 hypertension (The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure 1997). Blood cholesterol (CH) and triglycerides (TG) did not differ between groups (p = ns, ANOVA). The relationships between systolic (SBP) or diastolic (DBP) blood pressure and age, Wt, BMI, 4SF, WHR, TSR, CH and TG were independent from altitude (p = ns, ANCOVA). In the pooled sample (n = 374), age explained 1 and 3% of SBP (p &lt; 0:05) and DBP (p &lt; 0:005) variance respectively, Wt was the best predictor of SBP and DBP explaining 11 and 10% of their variance respectively (p &lt; 0:0001) and CH explained 5% of DBP variance (p &lt; 0:0001). In conclusion, hypertension is more frequent in LA- than MA- and HA-subjects from Central Asia. However, anthropometric characteristics and blood lipids do similarly contribute to explain blood pressure in these subjects.

An Bewohnern des Tieflandes (LA), mittlerer Hohen (MA) und an Hochlandbevolkerungen (HA) wurde der Zusammenhang zwischen dem Blutdruck, anthropometrischen Charakteristika und Blutlipiden untersucht. Im einzelnen handelt es sich bei den untersuchten Bevolkerungen um 72 LA-Uiguren (600m), 91 LA-Kirgis (900 m), 117 MA-Kasaks (2100 m) und 94 HA-Kirgis (3200 m). Es handelt sich ausschliesslich um mannliche Probanden ahnlichen Alters (p = ns, ANOVA; Variationsbreite fur alle 374 Probanden: 18-66 Jahre). Das Korpergewicht (Wt), der Body Mass Index (BMI) und die Summe von vier Hautfaltendicken (4SF) war bei den HA-Kirgis signifikant niedriger als in den ubrigen Gruppen (p &lt; 0:0005; p &lt; 0:0005 bzw. p &lt; 0:05, ANOVA). In der Verteilung des Korperfetts, die uber das Verhaltnis von Taillen- zu Huftumfang (WHR) sowie das Verhaltnis von Trizeps-Hautfaltendicke zur Dicke der subskapularen Hautfalte (TSR; p = ns, ANOVA) erfasst wurde, liessen sich jedoch keine Unterschiede beobachten. Ein Bluthochdruck im Stadium 1 liess sich bei 18% der LA-Uiguren, 2% der LA.Kirgis 4% der MA-Kasaks und 1% der HA-Kirgis beobachten; ein Bluthochdruck des Stadiums 2 wurde lediglich bei 2% der LA-Uiguren beobachtet, wahrend er in den ubrigen Bevolkerungen nicht vorkam; ein Bluthochdruck des Stadiums 3 wurde in keiner Bevolkerung beobachtet (The Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension 1997). In den Blutkonzentrationen von Cholesterin (CH) und Triglyzeriden (TG) wurden keine Unterschiede zwischen den Gruppen beobachtet (p = ns, ANOVA). Der Zusammenhang zwischen dem systolischen (SBP) bzw. dem diastolischen Blutdruck (DBP) und dem Alter, Wt, BMI, 4SF, WHR, TSR, CH und TG war von der Hohenlage des Wohnortes unabhangig (p = ns; ANCOVA). In der gepoolten Stichprobe (n = 374), erklarte das Alter 1 bzw. 3% der Varianz des SBP (p &lt; 0:05) bzw. des DBP (p &lt; 0:005). Das Gewicht erwies sich als bester Pradiktor des SBP und DBP, es erklarte 11 bzw. 10% der Varianz (p &lt; 0:0001). CH erklarte 5% der Varianz des DBP (p &lt; 0:0001). Zusammenfassend lasst sich festhalten, dass Bluthochdruck in Zentralasien bei LA-Bevolkerungen haufiger vorkommt als in MA- und HA-Bevolkerungen. Anthropometrische Charakteristika und Blutfette tragen jedoch in ahnlicher Weise zur Erklarung des Blutdruckes bei allen Probanden bei.

On a etudie les associations entre la pression arterielle, les caracteristiques anthropometriques et les lipides sanguins chez 72 Ouigour d'altitude basse (AB) (600 m), 91 AB-Khirghiz (900 m), 117 Kazakhs d'altitude moyenne (AM) (2100m) et 94 Kirghiz d'altitude haute (AH) (3200 m). Tous les sujets etaient des hommes adultes de moyenne d'age similaire (p = ns, ANOVA; etendue de variation pour l'ensemble des 374 sujets: 18-66 ans). Le poids corporel (Pds), l'indice de masse corporelle (IMC) et la somme des quatre plis cutanes (S4PC) etaient significativement plus bas chez les AH-Kirghiz que dans les autres groupes (respectivement p &lt; 0:0005, p &lt; 0:0005 et p &lt; 0:05 ANOVA). Cependant, on n'a pas trouve de difference dans la distribution de la graisse corporelle telle que determinee par les rapports des circonferences taille/hanches (RTH) et par le rapport des plis cutanes triceps/sous-scapulaire (RTS; p = ns, ANOVA). L'hypertension de niveau 1 est presente chez 18% des AB-Ouigour, 2% des AB-Kirghiz, 4% des AMKazakh et 1% des AH-Kirghiz. Le niveau 2 d'hypertension a ete detecte chez 2% des AB-Ouigour seulement. Aucun des sujets n'avait atteint le niveau 3 d'hypertension (Comite de Prevention, Detection, Evaluation et Traitement de la Haute Pression Arterielle, 1997). Le cholesterol sanguin (CS) et les triglycerides (TG) ne differaient pas entre groupes (p = ns, ANOVA). Les associations entre pressions arterielle systolique (PAS), diastolique (PAD) et l'age, le Pds, l'IMC, la S4PC, le RTH, le RTS, le CS et les TG sont independantes de l'altitude (p = ns, ANCOVA). L'age expliquait respectivement 1 et 3% des variances de la PAS (p &lt; 0:05) et de la PSD (p &lt; 0:005), le Pds etant le meilleur predicteur de la PAS et de la PAD, expliquant respectivement 11% et 10% de leur variance (p, &lt; 0:0001), le CS expliquant 5% de la variance en PAD (p &lt; 0:0001). En conclusion, l'hypertension est plus frequente chez les sujets d'AB- que d'AM- et d'AH- en Asie Centrale. Les caracteristiques anthropometriques et les lipides sanguins contribuent demaniere semblable a expliquer la pression arterielle chez les sujets examines.