Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2-4. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.
β‐catenin is a key protein in cadherin–catenin cell adhesion complex and its tyrosine phosphorylation is believed to cause destruction of junctional apparatus. The broad spectrum of substrates for kinases and phosphatases, however, does not rule out tyrosine phosphorylation of other junctional proteins as the main culprit in reduction of cell adhesion activity. Further, the endogenous β‐catenin perturbs detailed functional analysis of phosphorylated mutant β‐catenin in living cells. To directly evaluate the effect of β‐catenin tyrosine phosphorylation in cell adhesion, we utilized F9 cells in which expression of endogenous β‐catenin and its closely related protein plakoglobin were completely shut down. We also used α‐catenin‐deficient (αD) cells to evaluate the role of α‐catenin on β‐catenin tyrosine phosphorylation. We show that β‐catenin with phosphorylation mutation at 654th tyrosine forms functional cadherin–catenin complex to mediate strong cadherin‐mediated cell adhesion. Moreover, we show that 64th and 86th tyrosines are mainly phosphorylated in F9 cells, especially in the absence of α‐catenin. Phosphorylation of these tyrosine residues, however, does not affect cadherin‐mediated cell adhesion activity. Our data identified a novel site phosphorylated by endogenous tyrosine kinases in β‐catenin. We also demonstrate that tyrosine phosphorylation of β‐catenin might regulate cadherin‐mediated cell adhesion in a more complicated way than previously expected.
The objective of the study was to determine if the addition of topical antibiotic increases the efficacy of topical steroid in controlling otitis externa. A double-blind randomised controlled trial was performed from February 2003 to April 2005 in an otolaryngology emergency clinic (acute urban teaching hospital) in the United Kingdom. Patients were followed up for 2 weeks. Forty-five adults with otitis externa based on the presence of oedema, discharge or debris in the outer ear canal were recruited. The patients were randomised to one of the two treatment groups, namely using betamethasone sodium phosphate 0.1% (Vista-Methasone) or betamethasone sodium phosphate 0.1% with neomycin sulphate 0.5% (Vista-Methasone N), and were instructed to use the trial medication at three drops three times a day for 2 weeks. Subjects' visual analogue symptom scores (blockage, pain, discharge, and itching) for otitis externa pre-treatment (day 0) and post-treatment (day 15), percentage changes in visual analogue symptom scores as a result of treatment, proportion of patients whose symptom scores failed to improve or deteriorated on treatment were analysed. The two experimental arms demonstrated statistically similar presenting symptom scores at recruitment (mean symptom scores of 19.2 for betamethasone group and 28.7 for betamethasone-neomycin group). The mean symptom score change in response to treatment was 82.8 and 47.8% in the betamethasone-neomycin and betamethasone-alone groups, respectively. There was no statistically significant difference between the groups in median percentage symptom score change in response to treatment. All patients in the betamethasone-neomycin group showed symptom improvement but in the betamethasone alone group, five patients got worse (Fishers exact, P = 0.05). Topical antibiotic-steroid combination therapy is superior to steroid-alone treatment for symptomatic control of otitis externa.
We report the case of a 59-year-old man with a two-month history of a fast-growing, left-sided neck mass and a 5 mm nodule over a thyroid mass at the site of fine needle aspiration cytology performed four weeks earlier. Histopathological studies confirmed anaplastic carcinoma of the thyroid and cutaneous needle track seeding of the primary tumour. The patient succumbed to extensive disease 10 weeks after initial diagnosis. To our knowledge, this is a rare report of implantation of anaplastic thyroid carcinoma along the track of fine needle aspiration. Some factors involved in needle track seeding are: needle size; number of passes; withdrawing the needle without releasing suction; injecting the tumour at time of biopsy; and inherent characteristics of the lesion (e.g. number of cells dislodged, adhesiveness of cells, amount of stroma present, enzymes released and immunologic characteristics).
We present an uncomplicated case report of a cervical thoracic duct cyst (CTDC) in a 61-yearold woman treated with surgical excision. We reviewed 47 similar cases since it was first described in 1964 and evaluated the different diagnostic and management approaches. Previously believed to be the gold standard tool for evaluation, lymphangiography is now less popular due to advent of high-resolution imaging combined with aspiration techniques. CTDC treatment includes observation, low-fat diet, repeated aspirations, external pressure, sclerotherapy, embolisation, and surgical intervention. The preferred management of choice to date is surgical excision.
Introduction: Recent studies have reported that elevated levels of platelets and inflammatory markers are associated with poor treatment outcomes among patients with solid tumours, but reports are conflicting in head and neck cancer (HNC) patients. Objective: To establish if pre-treatment anti-inflammatory markers can be used as a prognostic tool of overall survival and tumour control among HNC patients. Methods: We retrospectively reviewed the pre-treatment platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) of 147 HNC patients from 2014 to 2018 and analysed their association with tumour progression and overall treatment outcomes. The optimal cutoff was established at > 200 for high PLR and > 2.85 for high NLR. Results: After adjusting for age, disease stage, and treatment, patients with higher PLR had an almost 3 times higher risk of mortality during the study period than patients with normal PLR (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.43-5.47, p < 0.01). Furthermore, the patients with higher NLR had an > 2.5 times higher risk of mortality than those with normal NLR (HR 2.62, 95% CI 1.19-5.81, p = 0.02). Conclusion: This observational study shows that elevated PLR and NLR in HNC patients, who were treated with either surgery or primarily chemoradiotherapy, are associated with poor overall survival.
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