In Vitro and In Vivo Effects of IGF-I on Adiposity in HIV-associated Metabolic Disease: A Pilot Study

AbstractMyriad difficulties exist in analyzing the pharmacology of the serotonin 1A (5-HT1A) receptor. The receptor may demonstrate a different activity depending on the tissue or species used for analysis, the agent used, laboratory conditions, and differences between in vitro and in vivo effects of compounds. Affinity for 5-HT receptors also varies widely, presenting difficulties in drawing definitive conclusions on affinity values for various compounds. At least two possibilities exist to explain the diversity of pharmacology of 5-HT receptors. First, it is possible that different 5-HT1A receptor subtypes exist. Second, the 5-HT1A receptors may play a far more complex role than previously believed.

Download Full-text

Creatine Supplementation for Patients with Inflammatory Bowl Diseases: A Scientific Rationale for a Clinical Trial

Nutrients ◽

10.3390/nu13051429 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1429

Author(s):

Theo Wallimann ◽

Caroline H. T. Hall ◽

Sean P. Colgan ◽

Louise E. Glover

Keyword(s):

Ulcerative Colitis ◽

Clinical Trial ◽

Crohn’S Disease ◽

Pilot Study ◽

Crohn's Disease ◽

Single Case ◽

Initial Period ◽

Creatine Supplementation

Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic cellular energy precursor, is likely to be effective in inducing a favorable response and/or remission in patients with inflammatory bowel diseases (IBD), like ulcerative colitis and/or Crohn’s disease”. A current pilot clinical trial that incorporates the use of oral Cr at a dose of 2 × 7 g per day, over an initial period of 2 months in conjunction with ongoing therapies (NCT02463305) will be informative for the proposed larger, more long-term Cr supplementation study of 2 × 3–5 g of Cr per day for a time of 3–6 months. This strategy should be insightful to the potential for Cr in reducing or alleviating the symptoms of IBD. Supplementation with chemically pure Cr, a natural nutritional supplement, is well tolerated not only by healthy subjects, but also by patients with diverse neuromuscular diseases. If the outcome of such a clinical pilot study with Cr as monotherapy or in conjunction with metformin were positive, oral Cr supplementation could then be used in the future as potentially useful adjuvant therapeutic intervention for patients with IBD, preferably together with standard medication used for treating patients with chronic ulcerative colitis and/or Crohn’s disease.

Download Full-text

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

Human & Experimental Toxicology ◽

10.1177/0960327121999454 ◽

2021 ◽

pp. 096032712199945

Author(s):

AT Aliyev ◽

S Ozcan-Sezer ◽

A Akdemir ◽

H Gurer-Orhan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Antitumor Effects ◽

Antiestrogenic Activity ◽

Er Positive ◽

In Vivo Effects ◽

Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

Download Full-text

Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion

Nutrients ◽

10.3390/nu13072223 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2223

Author(s):

Manon Dominique ◽

Nicolas Lucas ◽

Romain Legrand ◽

Illona-Marie Bouleté ◽

Christine Bôle-Feysot ◽

...

Keyword(s):

Food Intake ◽

Peptide Yy ◽

Molecular Mimicry ◽

Potential Effect ◽

In Vivo Studies ◽

Sprague Dawley ◽

E Coli ◽

In Vivo Effects

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague–Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

Download Full-text

Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

International Journal of Molecular Sciences ◽

10.3390/ijms22031347 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1347

Author(s):

Anaïs Amend ◽

Natalie Wickli ◽

Anna-Lena Schäfer ◽

Dalina T. L. Sprenger ◽

Rudolf A. Manz ◽

...

Keyword(s):

B Cell ◽

Disease Model ◽

Interleukin 10 ◽

Immune Functions ◽

Murine Lupus ◽

Anti Inflammatory ◽

In Vivo Effects

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

Download Full-text

Resizable Ventricular Patch Plasty in the Porcine Left Ventricle a Pilot Study

Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery ◽

10.1097/imi.0b013e3181cfa8f1 ◽

2010 ◽

Vol 5 (1) ◽

pp. 16-21 ◽

Cited By ~ 1

Author(s):

Willemijn H. F. Huijgen ◽

Paul F. Gründeman ◽

Tycho van der Spoel ◽

Maarten-Jan Cramer ◽

Paul Steendijk ◽

...

Keyword(s):

Pilot Study ◽

Animal Experiments ◽

Ventricular Volume ◽

Left Ventricular ◽

Left Ventricular Aneurysm ◽

Patch Shape ◽

End Diastolic Volume ◽

Patch Plasty

Objective Endoventricular circular patch plasty is a method used to reconstruct the ventricular cavity in patients with (post) ischemic left ventricular aneurysm or global dilatation. However, late redilatation with mitral regurgitation has been reported, in which postoperative apex shape seems to play an important role. We studied the feasibility of ventricular volume downsizing with a variably shaped patch in porcine hearts. Methods In five in vitro and two acute animal experiments, a dyskinetic aneurysm was simulated with a pericardial insert. Reducing patch surface by changing patch shape diminished end-diastolic volume. In vitro, static end-diastolic volume was determined for each patch shape using volumetry and echocardiography. In the acute animal experiments, preliminary observations of patch behavior in live material were made, and pressure/time relationship, dPdTmax, was registered. Results In vitro, bringing the convex patch into a flat plane reduced LV volume from 66 ± 7 mL (aneurysm) to 49 ± 5 mL. Four of 5 patch shapes further reduced volume to a mean of 38 ± 7 mL (P = 0.03). The in vitro echocardiographic measurements correlated with volumetry findings (r = 0.81). In the acute animal experiments, dPdTmax varied with patch shape, independent of volume changes. Conclusions In this pilot study, in vitro shape configuration of the resizable ventricular patch resulted in a calibrated end-diastolic volume reduction. The data of the two in vivo pilot experiments clearly indicate that change in patch configuration in the situation of more or less unchanged end-diastolic volume had impact on cardiac performance. Future studies must substantiate the results of this observation.

Download Full-text

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

Antioxidants ◽

10.3390/antiox9121210 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1210

Author(s):

Amy K. Hauck ◽

Tong Zhou ◽

Ambuj Upadhyay ◽

Yuxiang Sun ◽

Michael B. O’Connor ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Disease ◽

Adipose Tissue ◽

Fat Depots ◽

Michael Adducts ◽

Lipid Aldehydes ◽

Visceral Adipose ◽

Fat Feeding

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

Download Full-text

Role of Apolipoprotein A-I in Protecting against Endotoxin Toxicity

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/36.6.419 ◽

2004 ◽

Vol 36 (6) ◽

pp. 419-424 ◽

Cited By ~ 68

Author(s):

Juan Ma ◽

Xue-Ling Liao ◽

Bin Lou ◽

Man-Ping Wu

Keyword(s):

Survival Time ◽

Binding Capacity ◽

Density Lipoprotein ◽

Mtt Method ◽

Apolipoprotein A ◽

Plasma Fraction ◽

Significant Difference ◽

In Vivo Effects

Abstract High density lipoprotein (HDL) binds lipopolysaccharide (LPS or endotoxin) and neutralizes its toxicity. We investigated the function of Apolipoprotein A-I (ApoA-I), a major apolipoprotein in HDL, in this process. Mouse macrophages were incubated with LPS, LPS+ApoA-I, LPS+ApoA-I+LFF (lipoprotein-free plasma fraction d>1.210 g/ml), LPS+HDL, LPS+HDL+LFF, respectively. MTT method was used to detect the mortality of L-929 cells which were attacked by the release-out cytokines in LPS-activated macrophages. It was found that ApoA-I significantly decreased L-929 cells mortality caused by LPS treatment (LPS vs. LPS+ApoA-I, P<0.05) and this effect became even more significant when LFF was utilized (LPS vs. LPS+ApoA-I+LFF, P<0.01; LPS vs. LPS+HDL+LFF, P<0.01). There was no significant difference between LPS+ApoA-I+LFF and LPS+HDL+LFF treatment, indicating that ApoA-I was the main factor. We also investigated in vivo effects of ApoA-I on mouse mortality rate and survival time after LPS administration. We found that the mortality in LPS+ApoA-I group (20%) and in LPS+ApoA-I+LFF group (10%) was significantly lower than that in LPS group (80%) (P<0.05, P<0.01, respectively); the survival time was (43.20 ± 10.13) h in LPS+ApoA-I group and (46.80 ± 3.79) h in LPS+ApoA-I+LFF group, which were significantly longer than that in LPS group (16.25 ± 17.28) h (P<0.01). We also carried out in vitro binding study to investigate the binding capacity of ApoA-I and ApoA-I+LFF to fluorescence labeled LPS (FITC-LPS). It was shown that both ApoA-I and ApoA-I+LFF could bind with FITC-LPS, however, the binding capacity of ApoA-I+LFF to FITC-LPS (64.47 ± 8.06) was significantly higher than that of ApoA-I alone (24.35 ± 3.70) (P<0.01). The results suggest that: (1) ApoA-I has the ability to bind with and protect against LPS; (2) LFF enhances the effect of ApoA-I; (3) ApoA-I is the major contributor for HDL anti-endotoxin function.

Download Full-text