Regulation of granulocyte function by hyaluronic acid. In vitro and in vivo effects on phagocytosis, locomotion, and metabolism.

Polymer-based eye drops are the most used drug delivery system to treat dry eye disease (DED). Therefore, the mucoadhesion between the polymer and the ocular mucin is crucial to ensure the efficacy of the treatment. In this context, the present study aimed to evaluate the potential use of in vitro methods to study the mucoadhesion of eye drop solutions and, specifically to evaluate the efficacy of two hyaluronic acid-based formulations (HA), HA 0.15% and 0.30% (w/v) to treat DED. Rheology methods and zeta potential determination were used to study the mucoadhesive properties of both eye drop solutions. All results indicated that interactions occurred between the mucin and the HA, being stronger with HA 0.30%, due to the physical entanglements and hydrogen bounding. In vitro tests on ARPE-19 cell line were performed using a 2D and a 3D dry eye model and the results have shown that pre-treated cells with HA showed a morphology more similar to the hydrated cells in both products, with a high survival rate. The in vitro techniques used in this study have been shown to be suitable to evaluate and predict mucoadhesive properties and the efficacy of the eye drops on relief or treatment of DED. The results obtained from these methods may help in inferring possible in vivo effects.

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Pharmacology of 5-HT1A Receptors: Critical Aspects

CNS Spectrums ◽

10.1017/s1092852900006635 ◽

1998 ◽

Vol 3 (10) ◽

pp. 17-38 ◽

Cited By ~ 3

Author(s):

Franco Borsini

Keyword(s):

Receptor Subtypes ◽

Laboratory Conditions ◽

In Vivo Effects ◽

Critical Aspects

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.

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Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

Cell Death and Disease ◽

10.1038/s41419-021-03393-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wei Zhang ◽

Guoyu Yin ◽

Heping Zhao ◽

Hanzhi Ling ◽

Zhen Xie ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Hyaluronic Acid ◽

Dependent Manner ◽

Collagen Induced Arthritis ◽

Intracellular Degradation ◽

Main Pathway ◽

First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

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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.

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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.

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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.

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In vitro and in vivo effect of hyaluronic acid modified, doxorubicin and gallic acid co-delivered lipid-polymeric hybrid nano-system for leukemia therapy

Drug Design Development and Therapy ◽

10.2147/dddt.s202818 ◽

2019 ◽

Vol Volume 13 ◽

pp. 2043-2055 ◽

Cited By ~ 11

Author(s):

Yanping Shao ◽

Wenda Luo ◽

Qunyi Guo ◽

Xiaohong Li ◽

Qianqian Zhang ◽

...

Keyword(s):

Hyaluronic Acid ◽

Gallic Acid

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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.

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