mRNA aggregates harness danger response for potent cancer immunotherapy.

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA).

Nanoparticles as immunomodulators and translational agents in brain tumors.

Introduction: Brain tumors remain especially challenging to treat due to the presence of the blood-brain barrier. The unique biophysical properties of nanomaterials enable access to the tumor environment with minimally invasive injection methods such as intranasal and systemic delivery.

Methods: In this review, we will discuss approaches taken in NP delivery to brain tumors in preclinical neuro-oncology studies and ongoing clinical studies.

Indomethacin Increases Neurogenesis across Age Groups and Improves Delayed Probe Trial Difference Scores in Middle-Aged Rats.

We tested whether indomethacin or rosiglitazone treatment could rejuvenate spatial ability and hippocampal neurogenesis in aging rats. Young (4 mo; = 30), middle-aged (12 mo; = 31), and aged (18 mo; = 31) male Fischer 344 rats were trained and then tested in a rapid acquisition water maze task and then fed vehicle (500 μl strawberry milk), indomethacin (2.0 mg/ml), or rosiglitazone (8.

Communicating about the management of medications as patients move across transition points of care: an observation and interview study.

Rationale, Aims And Objectives: As patients move across transition points, effective medication management is critical for patient safety. The aims of this study were to examine how health professionals, patients and family members communicate about managing medications as patients moved across transition points of care and to identify possible sources of communication failure.

Method: A descriptive approach was used involving observations and interviews.

A new custom moldable external neck brace (ENB 2.0) to improve hands-free speech in laryngectomized patients.

Objectives/hypothesis: The majority of laryngectomy patients fail to use a hands-free valve on a daily basis, mainly due to fixation problems of the adhesive baseplate housing. To support adhesive housings during hands-free speech a new external neck brace (ENB 2.0) was developed.

Influence of a cervical mobilization technique on respiratory and cardiovascular function.

SUMMARY. Spinal manipulative therapy techniques are frequently applied by physiotherapists to relieve pain of musculo-skeletal origin and to improve the quality of joint movement in a variety of musculo-skeletal conditions. However, there has been little research into the physiological effects of these techniques, or the mechanisms responsible for these effects.

The effect of cholesterol oxidation products on human platelet aggregation.

The cholesterol oxidation products (oxysterols) cholest-3,5-diene-7-one, cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol (cholesterol 5 alpha-epoxide), cholestan-5 beta, 6 beta-epoxy-3 beta-ol (cholesterol 5 beta-epoxide), cholest-5-ene-3 beta-ol-7-one (7-ketocholesterol), cholest-5-ene-3 beta, 7 alpha-diol (7 alpha-hydroxycholesterol), cholestan-3 beta, 5 alpha, 6 beta-triol (cholestane triol), and cholest-5-ene-3 beta, 26-diol (27-hydroxycholesterol) potentiated platelet aggregation and increased thromboxane A2 formation in platelets challenged with thrombin, ADP or collagen. These effects were observed at oxysterol concentrations in the range 5-100 microM. Cholesterol 5 beta-epoxide and 7-ketocholesterol increased the mobilization of 3H-arachidonic acid from prelabelled platelet phospholipids in response to thrombin and collagen.

Dipyridamole inhibits the oxidative modification of low density lipoprotein.

The oxidative modification of low density lipoprotein (LDL) is believed to play an important role in the initiation of the atherosclerotic lesion. Dipyridamole, which is used clinically as a coronary vasodilator and an antiplatelet agent, has antioxidant properties. Probucol is a lipid-lowering agent which inhibits the oxidative modification of LDL.

Effect of anethole dithiolthione on human platelet aggregation.

Anethole dithiolthione (ADT) (10 mumol/l) inhibited platelet aggregation and the formation of thromboxane (Tx)B2 in plasma in response to adenosine diphosphate (ADP), epinephrine and arachidonic acid (AA). ADT partially inhibited platelet aggregation and TxB2 formation in plasma induced by thrombin, phorbol myristate acetate and calcium ionophore A23187 and increased the lag time of collagen-induced aggregation at concentrations in the range 10-40 mumol/l. ADT (100 mumol/l) completely inhibited the aggregation of washed platelets challenged with thrombin.

Effects of acrolein on human platelet aggregation.

Acrolein, a component of tobacco smoke, potentiated platelet aggregation and increased thromboxane A2 (TXA2) formation caused by thrombin and arachidonic acid (AA). Acrolein produced these effects at concentrations in the range 50-5000 microM. Acrolein had no effect on platelet responses to ADP, epinephrine, collagen or the ionophore A23187.

Platelet function and exercise-induced myocardial ischaemia in coronary heart disease patients.

Divergent reports of the effects of exercise-induced myocardial ischaemia on platelet function require clarification. This study examines the relationship between exercise, exertional myocardial ischaemia, and in vivo and ex vivo platelet function in 27 male patients, aged 35 to 69, with stable coronary heart disease (CHD). All medications were ceased at least 5 days prior to a maximal exercise test.

Determination of the lipid peroxidation product trans-4-hydroxy-2-nonenal in biological samples by high-performance liquid chromatography and combined capillary column gas chromatography-negative-ion chemical ionisation mass spectrometry.

trans-4-Hydroxy-2-nonenal (HNE) is an aldehyde end-product of lipid peroxidation in biological systems which is capable of producing a range of powerful biological effects. We wish to describe a sensitive and selective strategy for the determination of HNE in biological samples. The method is based on the formation of the O-pentafluorobenzyl (O-PFB) oxime derivatives of HNE and its deuterated internal standard which, after sample clean-up by solid-phase extraction and purification by high-performance liquid chromatography (HPLC), were derivatised further to trimethylsilyl ethers.

Effect of 4-hydroxy-2,3-trans-nonenal on platelet function.

4-Hydroxy-2,3-trans-nonenal (HNE), an aldehyde end-product of lipid peroxidation, potentiated aggregation and increased thromboxane A2 formation in platelets challenged with ADP, thrombin or the ionophore A23187. These effects were observed at HNE concentrations in the range 10-100 microM. Platelet responses to collagen, epinephrine and arachidonic acid were not affected by HNE.

Synergistic potentiation by epinephrine of collagen or thrombin-induced calcium mobilization in human platelets.

Changes in cytoplasmic free calcium in response to epinephrine in combination with other agonists were studied in human platelets loaded with the fluorescent calcium indicator, quin 2. In the presence of 1mM external calcium, epinephrine augmented the increase in cytoplasmic free calcium in response to collagen or thrombin, and this was inhibited by yohimbine. In the absence of extracellular calcium, thrombin and collagen only caused a small increase in cytoplasmic free calcium, and the response was not enhanced by epinephrine.

Daily release of copper from dental alloy restorations in a patient with Wilson's disease.

Wilson's disease is a rare genetic disorder in which copper accumulates in tissues. Its victims must adhere to a strict dietary regimen yielding less than 2 mg of copper per day. Three major variables have been identified as being of critical importance in the treatment of these patients: the amount of copper naturally occurring in foods, the amount of copper introduced during the preparation of foods, and the amount of copper in the environment.

Effect on human platelets of catecholamines at levels achieved in the circulation.

Epinephrine at concentrations varying between 3.3 and 12.5 nM had no effect on blood platelets when added alone, but augmented the in vitro platelet response to collagen and thrombin.

Effects of trifluoperazine on platelet activation.

Previous reports of the inhibitory effects of trifluoperazine on platelet responses to different aggregating agents have been conflicting, and the mechanism of action remains unclear. We have found that aggregation by minimum concentrations of collagen and arachidonic acid, and second phase aggregation by minimum concentrations of ADP, thrombin, epinephrine and the calcium ionophore A23187 were inhibited by 40-60 microM trifluoperazine. The first phase of aggregation by a minimum concentration of epinephrine was completely inhibited by 100 microM trifluoperazine, and the first phase of aggregation induced by ADP, thrombin or A23187 was decreased by 300 microM trifluoperazine.

Relation of angina to coronary artery disease in mitral and in aortic valve disease.

Of 129 patients with either mitral or aortic valve disease angina was present in 55 (42%). It was more frequent in aortic (60%) than in mitral valve disease (33%). The standard 12-lead electrocardiogram was not helpful in distinguishing underlying occlusive coronary artery disease.