Hyaluronic acid association with bacterial, fungal and viral infections: Can hyaluronic acid be used as an antimicrobial polymer for biomedical and pharmaceutical applications?

The relationships between hyaluronic acid (HA) and pathological microorganisms incite new understandings on microbial infection, tissue penetration, disease progression and lastly, potential treatments. These understandings are important for the advancement of next generation antimicrobial therapeutical strategies for the  control of healthcare-associated infections. Herein, this review will focus on the interplay between HA, bacteria, fungi, and viruses. This review will also comprehensively detail and discuss the antimicrobial activity displayed  by various HA molecular weights for a variety of biomedical and pharmaceutical applications, including  microbiology, pharmaceutics, and tissue engineering.  </p

<i>Ex vivo</i> basal production and relative induction of cytokines from NOD2 ligand activated PBMC in various groups.

<p>Culture supernatant was obtained from PBMCs cultured with medium or NOD2 ligand (Muramyl dipeptide, MDP) for 24 hours. The basal production (pg/ml) and relative induction (%) of cytokines (IL-1β, TNF-α, IL-6, IL-8 and IL-10) by PBMCs were analyzed by flow cytometry. Numerical data are expressed as median (interquartile range, IQR). Group 1) Patients with inactive disease (SLEDAI <4) who were never treated with immunosuppressants since the diagnosis or within the past 10 years, whichever longer; Group 2) Patients with inactive disease (SLEDAI <4) who had received or are currently on immunosuppressants; Group 3) Patients with active disease (SLEDAI >4) who had received or are currently on immunosuppressants.</p>&<p><i>p</i><0.05, comparing between Group 1 and Group 2;</p>Δ<p><i>p</i><0.05,</p>ΔΔΔ<p><i>p</i><0.001, comparing between Group 1 with healthy control subjects;</p>Φ<p><i>p</i><0.05,</p>ΦΦ<p><i>p</i><0.01, comparing between Group 2 with healthy control subjects;</p>§<p><i>p</i><0.05,</p>§§<p><i>p</i><0.01 comparing between Group 3 with healthy control subjects.</p

Expression of intracellular NOD2 in CD4⁺ T, CD8⁺ T, CD19⁺ B lymphocytes, monocytes, myeloid dendritic cells and plasmacytoid dendritic cells using flow cytometry.

<p>Group 1) Patients with inactive disease (SLEDAI <4) who were never treated with immunosuppressants since the diagnosis or within the past 10 years, whichever longer; Group 2) Patients with inactive disease (SLEDAI <4) who had received or are currently on immunosuppressants; Group 3) Patients with active disease (SLEDAI >4) who had received or are currently on immunosuppressants. The differential protein expression of intracellular pathogen recognition receptor NOD2 in (A) CD4+ T lymphocytes, (B) CD8+ T lymphocytes, (C) CD19+ B lymphocytes, (D) Monocytes, (E) myeloid dendritic cells (F) plasmacytoid dendritic cells of SLE patients and healthy controls by flow cytometry were shown as median (IQR) of mean fluorescence intensity (MFI) subtracting corresponding isotypic controls in scatter plots.</p

Demographic and clinical characteristics of patients with systemic lupus erythematosus.

<p>Values are median (interquartile range, IQR) unless stated otherwise; s.d., standard deviation; n.a., not applicable. SLE, systemic lupus erythematosus; Group 1) Patients with inactive disease (SLEDAI <4) who were never treated with immunosuppressants since the diagnosis or within the past 10 years, whichever longer; Group 2) Patients with inactive disease (SLEDAI <4) who had received or are currently on immunosuppressants; Group 3) Patients with active disease (SLEDAI >4) who had received or are currently on immunosuppressants. SLEDAI, systemic lupus erythematosus disease activity index; SLICC, Systemic Lupus International Collaborating Clinics Score;</p>┼<p>“Never” refers to SLE patients never be given treatment of immunosuppressants [prednisolone, hydroxychloroquine, azathioprine, cyclophosphamide (oral or IV), cyclosporin A and mycophenolate mofetil] since the diagnosis of SLE or within recent 10 years;</p>┼┼<p>“Ever” refer to use of immunosuppressants since the diagnosis of SLE.</p>┼┼┼<p>“<i>Flare</i>” is defined as increase in the SLEDAI score by 3 or more;</p>&<p><i>p</i><0.05,</p>&&<p><i>p</i><0.01,</p>&&&<p><i>p</i><0.001, comparing between Group 1 and Group 2;</p><p>*<i>p</i><0.05,</p><p>**<i>p</i><0.01,</p><p>***<i>p</i><0.001, comparing between Group 1 and Group 3;</p>#<p><i>p</i><0.05,</p>##<p><i>p</i><0.01,</p>###<p>p<0.001, comparing between Group 2 and Group 3.</p

Univariate analysis: the relationship between clinical characteristics, the use of drugs ever and the expression of NOD2 in SLE patients (categorical variables).

┼<p>“<i>Flare</i>” is defined as increase in the SLEDAI score by 3 or more;</p>┼┼<p>“Ever” refers to use of immunosuppressants [prednisolone, hydroxychloroquine, azathioprine, cyclophosphamide (oral or IV), cyclosporin A and mycophenolate mofetil] since the diagnosis of SLE;</p><p>*<i>p</i><0.05.</p

Additional file 2: of Sheng Jiang San, a traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidase inhibition and immune regulation

Figure S1. HPLC analysis of SJS (a) HPLC profile of SJS (b) Some constituents were denoted by standard compounds. (PPTX 128 kb

Additional file 1: of Sheng Jiang San, a traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidase inhibition and immune regulation

Method of High-performance liquid chromatography (HPLC) analysis of SJS. HPLC method was used to analyze the chemical profile of SJS. The HPLC condition is described in this additional file and the profile is shown in Additional file 2: Figure S1. By comparing with reference compounds, rhein, chrysophanol, emodin, aloe emodin and curcumin were found. (DOCX 13 kb

Source of IL-6, CXCL1, CXCL8, CXCL10, CCL2 and CCL5 in co-culture of eosinophils and fibroblasts under IL-31 and IL-33 stimulation.

<p>Eosinophils (3×10⁵ cells) and confluent fibroblasts (1×10⁵ cells) were treated with or without 1% paraformaldehyde for 1 h on ice prior to being cultured together with or without IL-31 and/or IL-33 (50 ng/ml) for 24 h. Cytokines and chemokines released in culture supernatant were determined by either CBA or Bio-plex pro assay. Results are expressed as the arithmetic mean plus SD of three independent experiments. E: unfixed eosinophils; E∧: fixed eosinophils; F: unfixed dermal fibroblasts; F∧: fixed dermal fibroblasts *p<0.05 when compared with corresponding unfixed control.</p

Effect of transwell inserts on the induction of IL-6, CXCL1, CXCL8, CXCL10, CCL2 and CCL5 in co-culture of eosinophils and fibroblasts under IL-31 and IL-33 stimulation.

<p>Eosinophils (3×10⁵ cells) and confluent fibroblasts (1×10⁵ cells) were cultured together with or without IL-31 and/or IL-33 (50 ng/ml) in the presence or absence of transwell inserts for 24 h. Cytokines and chemokines released in culture supernatant were determined by either CBA or Bio-plex pro assay. Results are expressed as the arithmetic mean plus SD of three independent experiments. EF: co-culture of eosinophils and dermal fibroblasts *p<0.05 when compared with corresponding control without transwell insert.</p

Effects of signaling molecule inhibitors on the release of IL-6, CXCL1, CXCL8, CXCL10, CCL2 and CCL5 from co-culture of eosinophils and fibroblasts with or without IL-31 and IL-33 stimulation.

<p>Eosinophils (3×10⁵ cells) cultured together with confluent fibroblasts (1×10⁵ cells) were pretreated with BAY11-7082 (1 µM), LY294002 (5 µM), U0126 (10 µM), SP600125 (3 µM) or SB203580 (7.5 µM) for 45 min, followed by incubation with or without IL-31 or IL-33 (50 ng/ml) in the presence of inhibitors for further 24 h. Released cytokines and chemokines in culture supernatant were determined by either CBA or Bio-plex pro assay. Results are expressed as the arithmetic mean plus SD of three independent experiments. DMSO (0.1%) was used as the vehicle control. Ctrl: medium control; BAY: BAY11-7082, LY: LY294002, U: U0126, SB: SB203580, SP: SP600125 *p<0.05 when compared between treatment group and control cell group.</p