MiR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression, macrophage activation, and foam cell formation.

Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κß) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses. First, the miR-146a encapsulated liposomes showed uniform size (radius 96.4 ± 4.22 nm) and round shape, long term stability (at least two months), high encapsulation efficiency (69.73 ± 0.07%), and were well transfected to human aortic endothelial cells (HAECs), human aortic smooth muscle cells (SMCs), and human differentiated monocytes (U937 cells). In addition, we demonstrated that miR-146a encapsulated liposomes reduced vascular inflammation responses in HAECs and SMCs through inhibition of ICAM-1 expression and decreased monocyte adhesion. In macrophages, miR-146a liposome treatment demonstrated decreased production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), as well as reduced oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation. Thus, based on these results, miR-146a encapsulated liposomes may be promising for reducing vascular inflammation by targeting its multiple associated mediators.

Evaluation of children's pain expression and behavior using audio visual distraction.

OBJECTIVES: Dental anxiety distresses children and their families with consequent poor oral health and costly pediatric dental services. Children's behaviors could be modified using a distraction technique for improved dental treatment. The study evaluates the effects of an audio-visual distraction on children's behaviors and pain expressions during dental treatment. MATERIAL AND METHODS: One hundred healthy children, between 4 and 6 years of age, were randomly assigned to one of two groups: audio visual distraction (AVD, N = 61) group and control (CTR, N = 39) group. The pre and post pain expression was collected using a faces pain rating scale from the participated children. Children's behavior was evaluated using the Frankl behavior rating scale by the assigned dentist. Data was analyzed using chi-squared tests and analysis of variance. RESULTS: The AVD group demonstrated more "definitely positive" behavior (91.8%) compared to the CTR group (35.9%) based on the Frankl scale evaluation from pre- and post-treatment (p < 0.0001). The pain rating scale did not demonstrate a significant difference in post-treatment pain scales (p = 0.2073) or changes in pain (p = 0.1532) between the AVD group and CTR group. CONCLUSIONS: The AVD is an effective distraction tool for young children during dental treatment regardless of child's subjective pain expression.

Nutraceutical based SIRT3 activators as therapeutic targets in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and its incidence is increasing worldwide with increased lifespan. Currently, there is no effective treatment to cure or prevent the progression of AD, which indicates the need to develop novel therapeutic targets and agents. Sirtuins, especially SIRT3, a mitochondrial deacetylase, are NAD-dependent histone deacetylases involved in aging and longevity. Accumulating evidence indicates that SIRT3 dysfunction is strongly associated with pathologies of AD, hence, therapeutic modulation of SIRT3 activity may be a novel application to ameliorate the pathologies of AD. Natural products commonly used in traditional medicine have wide utility and appear to have therapeutic benefits for the treatment of neurodegenerative diseases such as AD. The present review summarizes the currently available natural SIRT3 activators and their potentially neuroprotective molecular mechanisms of action that make them a promising agent in the treatment and management of neurodegenerative diseases such as AD.

Recent Progress in in vitro Models for Atherosclerosis Studies.

Atherosclerosis is the primary cause of hardening and narrowing arteries, leading to cardiovascular disease accounting for the high mortality in the United States. For developing effective treatments for atherosclerosis, considerable efforts have been devoted to developing in vitro models. Compared to animal models, in vitro models can provide great opportunities to obtain data more efficiently, economically. Therefore, this review discusses the recent progress in in vitro models for atherosclerosis studies, including traditional two-dimensional (2D) systems cultured on the tissue culture plate, 2D cell sheets, and recently emerged microfluidic chip models with 2D culture. In addition, advanced in vitro three-dimensional models such as spheroids, cell-laden hydrogel constructs, tissue-engineered blood vessels, and vessel-on-a-chip will also be covered. Moreover, the functions of these models are also summarized along with model discussion. Lastly, the future perspectives of this field are discussed.

Endothelium-Mimicking Nanomatrix Coating to Enhance Endothelialization after Left Atrial Appendage Closure Device Implantation.

Blood clots (90%) originate from the left atrial appendage (LAA) in non-valvular atrial fibrillation patients and are a major cause of embolic stroke. Long-term anticoagulation therapy has been used to prevent thrombus formation, but its use is limited in patients at a high risk for bleeding complications. Thus, left atrial appendage closure (LAAC) devices for LAA occlusion are well-established as an alternative to the anticoagulation therapy. However, the anticoagulation therapy is still required for at least 45 days post-implantation to bridge the time until complete LAA occlusion by neoendocardium coverage of the device. In this study, we applied an endothelium-mimicking nanomatrix to the LAAC device membrane for delivery of nitric oxide (NO) to enhance endothelialization, with the goal of possibly being able to reduce the duration of the anticoagulation therapy. The nanomatrix was uniformly coated on the LAAC device membranes and provided sustained release of NO for up to 1 month in vitro. In addition, the nanomatrix coating promoted endothelial cell proliferation and reduced platelet adhesion compared to the uncoated device membranes in vitro. The nanomatrix-coated and uncoated LAAC devices were then deployed in a canine LAA model for 22 days as a pilot study. All LAAC devices were not completely covered by neoendocardium 22 days post-implantation. However, histology image analysis showed that the nanomatrix-coated LAAC device had thicker neoendocardium coverage compared to the uncoated device. Therefore, our in vitro and in vivo results indicate that the nanomatrix coating has the potential to enhance endothelialization on the LAAC device membrane, which could improve patient outcomes by shortening the need for extended anticoagulation treatment.

Pulp-Dentin Tissue Healing Response: A Discussion of Current Biomedical Approaches.

Dental pulp tissue exposed to mechanical trauma or cariogenic process results in root canal and/or periapical infections, and conventionally treated with root canal procedures. The more recent regenerative endodontic procedure intends to achieve effective root canal disinfection and adequate pulp-dentin tissue regeneration; however, numerous limitations are reported. Because tooth is composed of vital soft pulp enclosed by the mineralized hard tissue in a highly organized structure, complete pulp-dentin tissue regeneration has been challenging to achieve. In consideration of the limitations and unique dental anatomy, it is important to understand the healing and repair processes through inflammatory-proliferative-remodeling phase transformations of pulp-dentin tissue. Upon cause by infectious and mechanical stimuli, the innate defense mechanism is initiated by resident pulp cells including immune cells through chemical signaling. After the expansion of infection and damage to resident pulp-dentin cells, consequent chemical signaling induces pluripotent mesenchymal stem cells (MSCs) to migrate to the injury site to perform the tissue regeneration process. Additionally, innovative biomaterials are necessary to facilitate the immune response and pulp-dentin tissue regeneration roles of MSCs. This review highlights current approaches of pulp-dentin tissue healing process and suggests potential biomedical perspective of the pulp-dentin tissue regeneration.

Candida Infection Associated with Salivary Gland-A Narrative Review.

Candida species are common global opportunistic pathogens that could repeatedly and chronically cause oral mucosa infection and create an inflammatory environment, leading to organ dysfunction. Oral Candida infections may cause temporary or permanent damage to salivary glands, resulting in the destruction of acinar cells and the formation of scar tissue. Restricted function of the salivary glands leads to discomfort and diseases of the oral mucosa, such as dry mouth and associated infection. This narrative review attempts to summarize the anatomy and function of salivary glands, the associations between Candida and saliva, the effects of Candida infection on salivary glands, and the treatment strategies. Overall, clinicians should proactively manage Candida infections by educating patients on oral hygiene management for vulnerable populations, conducting frequent checks for a timely diagnosis, and providing an effective treatment plan.

SIRT3 activator Honokiol attenuates ß-Amyloid by modulating amyloidogenic pathway.

Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aß), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer's disease (AD) and is related to the development of cognitive impairment and neuronal cell death. Aß is generated from amyloid-ß precursor protein (APP) through sequential cleavages, first by ß-secretase and then by γ-secretase. Drugs modulating this pathway are believed to be one of the most promising strategies for AD treatment. In the present study, we found that Honokiol significantly enhanced SIRT3 expression, reduced reactive oxygen species generation and lipid peroxidation, enhanced antioxidant activities, and mitochondrial function thereby reducing Aß and sAPPß levels in Chinese Hamster Ovarian (CHO) cells (carrying the amyloid precursor protein-APP and Presenilin PS1 mutation). Mechanistic studies revealed that Honokiol affects neither protein levels of APP nor α-secretase activity. In contrast, Honokiol increased the expression of AMPK, CREB, and PGC-1α, thereby inhibiting ß-secretase activity leading to reduced Aß levels. These results suggest that Honokiol is an activator of SIRT3 capable of improving antioxidant activity, mitochondrial energy regulation, while decreasing Aß, thereby indicating it to be a lead compound for AD drug development.