pH-triggered decomposition of polymeric fluorescent vesicles to induce growth of tetraphenylethylene nanoparticles for long-term live cell imaging

Publication date: 2 June 2017
Source:Polymer, Volume 118
Author(s): Xing Wang, Yanyu Yang, Fei Yang, Hong Shen, Decheng Wu
Self-assembly schemes provide a simple and tunable approach to creating a myriad of well-defined nanostructures from design of macromolecules in bulk, thin film and solution environments. Here we demonstrated a facile method to construction of tetraphenylethylene nanoparticles (TPE NPs) by decomposition-assembly from pH-responsive and AIE-characteristic vesicles, which were self-assembled by an amphiphilic PEG750-POSS-(TPE)7 polymer in aqueous solutions. The introduction of Schiff base bonds furnished the fluorescent polymersomes with unique pH responsiveness that is stable under physiological conditions but quickly degradable in acidic environments. Interestingly, the luminous vesicles were transformed into spherical TPE NPs in a solution of lower pH on account of the synergetic combination of cleavage rate of the Schiff base bonds and guidance effect of the entangled tadpole-shaped polymeric chains. The AIE feature of TPE molecule was completely retained in the TPE NPs. Compared to the pH-responsive PEG750-POSS-(TPE)7 vesicles, these AIE-active TPE NPs possessed stable morphology and adjustable size by manipulation of the incubation time. These TPE NPs can be quickly internalized into the tumors through endocytosis pathway and retain strong blue luminescence inside the living cells for a long period, presenting the good photostability and biological imaging property. Cytotoxicity assay revealed that TPE NPs were biocompatible and thus can be utilized for long-term live cell imaging and biomedical applications.

Graphical abstract

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A systematic review and narrative synthesis of interventions for uncomplicated obesity: weight loss, well-being and impact on eating disorders

Abstract

Objective

Most weight loss research focuses on weight as the primary outcome, often to the exclusion of other physiological or psychological measures. This study aims to provide a holistic evaluation of the effects from weight loss interventions for individuals with obesity by examining the physiological, psychological and eating disorders outcomes from these interventions.

Methods

Databases Medline, PsycInfo and Cochrane Library (2011–2016) were searched for randomised controlled trials and systematic reviews of obesity treatments (dietary, exercise, behavioural, psychological, pharmacological or surgical). Data extracted included study features, risk of bias, study outcomes, and an assessment of treatment impacts on physical, psychological or eating disorder outcomes.

Results

From 3628 novel records, 134 studies met all inclusion criteria and were evaluated in this review. Lifestyle interventions had the strongest evidence base as a first-line approach, with escalation to pharmacotherapy and bariatric surgery in more severe or complicated cases. Quality of life was the most common psychological outcome measure, and improved in all cases where it was assessed, across all intervention types. Behavioural, psychological and lifestyle interventions for weight loss led to improvements in cognitive restraint, control over eating and binge eating, while bariatric surgery led to improvements in eating behaviour and body image that were not sustained over the long-term.

Discussion

Numerous treatment strategies have been trialled to assist people to lose weight and many of these are effective over the short-term. Quality of life, and to a lesser degree depression, anxiety and psychosocial function, often improve alongside weight loss. Weight loss is also associated with improvements in eating disorder psychopathology and related measures, although overall, eating disorder outcomes are rarely assessed. Further research and between-sector collaboration is required to address the significant overlap in risk factors, diagnoses and treatment outcomes between obesity and eating disorders.

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Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy

Publication date: July 2017
Source:Biomaterials, Volume 134
Author(s): Lanlan Liu, Huqiang Yi, Huamei He, Hong Pan, Lintao Cai, Yifan Ma
Repolarizing Tumor-associated macrophages (TAMs) to anti-tumor M1 macrophages with microRNA (miR) is a plausible approach for cancer treatment. However, how to achieve TAM-targeted miR delivery remains a challenge. The present study generated redox/pH dual-responsive hybrid polypeptide nanovectors, which consisted of self-crosslinked redox-responsive nanoparticles based on galactose-functionalized n-butylamine-poly(l-lysine)-b-poly(l-cysteine) polypeptides (GLC) coated with DCA-grafted sheddable PEG-PLL (sPEG) copolymers. The ex vivo study showed that sPEG shielded cationic GLC core at physiological pH but quickly shed off to re-expose GLC due to it charge reversible property. Encapsulation with sPEG/GLC nanovectors effectively facilitated macrophage-targeted miR delivery at the acidic condition but diminished miR uptake at neutral pH. Administration of miR155-loaded sPEG/GLC (sPEG/GLC/155) nanocomplexes increased miR155 expression in TAMs about 100–400 folds both in vitro and in vivo. sPEG/GLC/155 also effectively repolarized immunosuppressive TAMs to anti-tumor M1 macrophages through elevating M1 macrophage markers (IL-12, iNOS, MHC II) and suppressing M2 macrophage markers (Msr2 and Arg1) in TAMs. Moreover, the treatment of sPEG/GLC/155 significantly increased activated T lymphocytes and NK cells in tumors, which consequently led to robust tumor regression. Hence, TAM-targeted delivery of miR with redox/pH dual-responsive sPEG/GLC nanovectors could be a promising approach to re-polarize TAMs to M1 macrophages in situ and induce tumor regression.



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A Study of Single Nucleotide Polymorphisms of Tumour Necrosis Factor α-1031 And Tumour Necrosis Factor β+ 252 in Chronic Rhinosinusitis.

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A Study of Single Nucleotide Polymorphisms of Tumour Necrosis Factor α-1031 And Tumour Necrosis Factor β+ 252 in Chronic Rhinosinusitis.

Clin Exp Otorhinolaryngol. 2017 Apr 28;:

Authors: Misron K, Hamid SSA, Ahmad A, Ramli RR

Abstract
Objectives: This case-controlled study aimed to identify the association of tumor necrosis factor (TNF)α-1031 and TNFβ+252 gene polymorphisms between chronic rhinosinusitis (CRS) and healthy controls. Another purpose of this study was to investigate the associations of these gene polymorphisms with factors related to CRS.
Methods: All deoxyribonucleic acid (DNA) samples were genotyped for TNFα-1031 and TNFβ+252 genes by mean of polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP). The statistical analysis were carried out using chi-square test or Fisher exact test to determine the associations of these gene polymorphisms in CRS. Multiple logistic regression was performed to evaluate the associations of these gene polymorphisms in CRS and its related risk factors.
Results: The genotype and allele frequencies of TNFα-1031 and TNFβ+252 gene did not show any significant associations between CRS and healthy controls. However, a significantly statistical difference of TNFα-1031 was observed in CRS participants with atopy (P-value, 0.045; odds ratio, 3.66) but not in CRS with asthma or aspirin intolerance.
Conclusion: Although the presence of TNFα-1031 and TNFβ+252 gene polymorphisms did not render any significant associations between CRS and healthy control, this study suggests that TNFα-1031 gene polymorphisms in CRS patients with atopy may be associated with increase susceptibility towards CRS.

PMID: 28449554 [PubMed - as supplied by publisher]

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Changes in the Reflux Symptom Index After Multilevel Surgery for Obstructive Sleep Apnea.

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Changes in the Reflux Symptom Index After Multilevel Surgery for Obstructive Sleep Apnea.

Clin Exp Otorhinolaryngol. 2017 Apr 28;:

Authors: Kim SJ, Kim HY, Jeong JI, Hong SD, Chung SK, Dhong HJ

Abstract
Objectives: This study evaluated whether the symptoms of laryngopharyngeal reflux (LPR) change after multilevel surgery for obstructive sleep apnea (OSA).
Methods: Patients who underwent multilevel surgery for OSA between April 2009 and September 2014 were enrolled in this study. All patients underwent preoperative polysomnography prior to surgery and were asked to complete the reflux symptom index (RSI) questionnaire before and after surgery.
Results: Of 73 enrolled patients, 24 (33%) reported an RSI score >13 and were thus classified as having reflux. The mean RSI score before surgery was 11.48±7.95; this number decreased to 4.95±6.19 after surgery (P<0.001). The rate of positive RSI responses was 33% before surgery and 9% after surgery. Each variable that comprised the RSI improved significantly after surgery, except for difficulty with swallowing. Regarding the degree of RSI improvement after surgery, there were no significant differences between subgroups according to sex, age, body mass index, OSA severity, or surgical outcome.
Conclusion: LPR symptoms are prevalent in OSA patients. Treatment for OSA using multilevel surgery potentially reduces the symptoms of LPR.

PMID: 28449553 [PubMed - as supplied by publisher]

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Effect of Proparacaine in a Mouse Model of Allergic Rhinitis.

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Effect of Proparacaine in a Mouse Model of Allergic Rhinitis.

Clin Exp Otorhinolaryngol. 2017 Apr 28;:

Authors: Kim HS, Won S, Lee EK, Chun YH, Yoon JS, Kim JT, Kim HH

Abstract
Objectives: Lidocaine, a local anaesthetic is a treatment option in uncontrolled asthma due to its immunomodulatory effects. In the present study, proparacaine (PPC), a derivative of lidocaine was examined for its therapeutic application in a mouse model of allergic rhinitis.
Methods: The mice were grouped into 4 groups: control group, allergic rhinitis (AR) group, ciclesonide (CIC) group, and PPC group. Nasal symptom scores, eosinophil counts, goblet cell counts, and mast cells counts in the nasal mucosa were measured. Serum ovalbumin (OVA)-specific immunoglobulin (Ig) E, OVA-specific IgG1, OVA-specific IgG2a, interleukin (IL)-4, IL-5, and cortisol levels were measured.
Results: Intranasal administration of PPC significantly decreased nasal symptoms, number of eosinophils, goblet cells, and mast cells in the lamina propria of the nasal mucosa. Serum OVA-specific IgE, OVA-specific IgG1, OVA-specific IgG2a was significantly higher in the AR compared with the control group. Serum level of IL-4 was significantly lower in the CIC group and PPC group in comparison with AR group. Serum IL-5 showed no significant difference among all groups. No significant difference in serum cortisol levels was observed among the 4 groups.
Conclusion: PPC appears to have a therapeutic potential in treatment of allergic rhinitis in a mouse model by reducing eosinophil, goblet cell, and mast cell infiltration in the nasal mucosa.

PMID: 28449552 [PubMed - as supplied by publisher]

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A Survey of Korean Physicians' Prescription Patterns for Allergic Rhinitis.

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A Survey of Korean Physicians' Prescription Patterns for Allergic Rhinitis.

Clin Exp Otorhinolaryngol. 2017 Apr 28;:

Authors: Seo MY, Kim DK, Jee HM, Ahn YM, Kim YM, Hong SD, Work Group for Allergic Rhinitis of the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI)

Abstract
Objectives: The aim of this study was to compare the prescription patterns according to characteristics of physicians using a survey distributed amongst physicians in Korea.
Methods: We surveyed the prescription patterns for allergic rhinitis (AR) of the members of the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI) and the Korean Association of Otorhinolaryngologists (KAO). Questionnaire contained 4 categories with 28 queries. 448 physicians including 98 internal medicine (IM), 113 pediatrics (PED), and 237 otorhinolaryngology (ENT) were responded.
Results: Although the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines are most frequently used in all specialties, seasonal or perennial AR is the most frequent classification system. For the definitive diagnosis of AR, ENT physicians reported using multiple allergen simultaneous test (MAST)/radio allergy sorbent test (RAST) more than others (IM, 10.9%; PED, 20.6%; ENT, 44.2%; P<0.001). In treatment, most physicians reported that antihistamine medication is the initial treatment for AR. PED physicians prescribed fewer intranasal steroid to combinations with an antihistamine than other specialists (IM, 65.3%; PED, 42.5%; ENT, 63.3%), but preferred leukotriene antagonists (IM, 4.1%; PED, 23.0%; ENT, 3.9%; P=0.041). Overall, 53% (235/448) of the physicians performed allergen immunotherapy (AIT), and IM administers the most AIT (IM, 71.6%; PED, 42.0%; ENT, 39.5%; P=0.019). Furthermore, university and general hospital physicians prescribed more AIT than doctors at other hospital types (university hospital, 76.4%; general hospital, 64.3%; local hospital, 21.4%; private clinic, 20.2%; P<0.001).
Conclusion: The prescription patterns for AR were different according to the physicians' characteristics and general rate of prescribing AIT is just about 53% in Korea. Thus, the development of complementary Korean-specific guidelines is needed and proper clinical instruction of AIT would be necessary.

PMID: 28449551 [PubMed - as supplied by publisher]

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