8 research outputs found
Lymphatic Function in Autoimmune Diseases
Lymphatic vessels are critical for clearing fluid and inflammatory cells from inflamed tissues and also have roles in immune tolerance. Given the functional association of the lymphatics with the immune system, lymphatic dysfunction may contribute to the pathophysiology of rheumatic autoimmune diseases. Here we review the current understanding of the role of lymphatics in the autoimmune diseases rheumatoid arthritis, scleroderma, lupus, and dermatomyositis and consider the possibility that manual therapies such as massage and acupuncture may be useful in improving lymphatic function in autoimmune diseases
Design and syntheses of highly potent teixobactin analogues against Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) in vitro and in vivo
The cyclic depsipeptide, teixobactin kills a number of Gram positive bacteria including Methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis without detectable resistance. To date, teixobactin is the only molecule in its class which has shown in vivo antibacterial efficacy. There have been no in vivo evaluation studies on teixobactin analogues. In this work, we have designed and synthesized 10 new in vivo ready teixobactin analogues. These analogues showed highly potent antibacterial activity against Staphylococcus aureus, MRSA, and vancomycin-resistant Enterococci (VRE) in vitro. One analogue, D-Arg4-Leu10-teixobactin 2 was found to be non-cytotoxic in vitro and in vivo. Most importantly, in a mice model of S. aureus keratitis, topical instillation of peptide 2 decreased the bacterial bioburden (>99.0% reduction) and corneal edema significantly when compared to untreated cornea. Collectively, our results establish the excellent therapeutic potential of teixobactin analogue in attenuating bacterial infections and the associated severities
Highly Efficient Supramolecular Aggregation-Induced Emission-Active Pseudorotaxane Luminogen for Functional Bioimaging
The
direct tracking of cells using fluorescent dyes is a constant
challenge in cell therapy due to aggregation-induced quenching (ACQ)
effect and biocompatibility issues. Here, we demonstrate the development
of a biocompatible and highly efficient aggregation-induced emission
(AIE)-active pseudorotaxane luminogen based on tetraphenylethene conjugated
polyÂ(ethylene glycol) (TPE-PEG<sub>2</sub>) (guest) and α-cyclodextrin
(α-CD) (host). It is capable of showing significant fluorescent
emission enhancement at the 400–600 nm range when excited at
388 nm, without increasing the concentration of AIE compound.
The fluorescent intensity of TPE-PEG<sub>2</sub> solution was effectively
enhanced by 4–12 times with gradual addition of 1–4
mM of α-CD. 2D NOSEY <sup>1</sup>H NMR revealed clear correlation
spots between the characteristic peaks of α-CD and PEG, indicating
the interaction between protons of ethylene glycol and cyclodextrin,
and the structures are mainly based on threaded α-CD. The host–guest
complex exhibits boosted fluorescent emission because the PEG side
chains are confined in “nano-cavities” (host), thus,
applying additional restriction on intermolecular rotation of TPE
segments. <i>In vitro</i> cell experiments demonstrated
the potential of AIE-active pseudorotaxane polymer as a biocompatible
bioimaging probe
Nogo-A reduces ceramide de novo biosynthesis to protect from heart failure
Growing evidence correlate the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in the vascular wall, down-regulates the sphingolipid de novo biosynthesis, via serine palmitoyltransferase (SPT), first and rate liming enzyme, to impact vascular functions and blood pressure. Nogo-A, a splice isoform of Nogo, is transiently expressed in cardiomyocyte (CM) following pressure overload. Cardiac Nogo is upregulated in dilated and ischemic cardiomyopathies in animals and humans. However, its biological function in the heart remains unknown