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Here, a highly cooperative liquid metal nanoparticle-enzyme (LM@GOX) was constructed for combinational starvation/photothermal therapy of tumor. It was found that the enzyme activity of glucose oxidase (GOX) could be strengthened along with the increased temperature within a given range and its optimal activity is around about 43-60 °C. Utilizing the photothermal conversion ability of liquid metal (LM), the GOX catalytic efficiency could be photo-controlled with improved starvation therapeutic efficiency. Furthermore, due to the accelerating blood flow during the photothermal therapy (PTT), the hypoxic situation in tumor tissues could also be relieved, which would contribute to conquering the hypoxia-suppressed GOX catalysis. In the meanwhile, the severe thermo-resistance of tumor cells during PTT process could be overcome by GOX induced decrease of adenosine triphosphate (ATP) and heat shock proteins (HSPs) level, eventually leading to an improved therapeutic effect of PTT. Both in vitro and in vivo studies proved that LM@GOX could significantly inhibit the growth of solid tumor under NIR illumination by a win-win cooperative starvation/photothermal therapy.
The gastrointestinal (GI) tract harbors commensal microorganisms as well as invasive bacteria, toxins and other pathogens and, therefore, plays a pivotal barrier and immunological role against pathogenic agents. The vagus nerve is an important regulator of the GI tract-associated immune system, having profound effects on inflammatory responses. Among GI tract organs, the liver is a key site of immune surveillance, as it has a large population of resident macrophages and receives the blood drained from the guts through the hepatic portal circulation. Although it is widely accepted that the hepatic tissue is a major target for vagus nerve fibers, the role of this neural circuit in liver immune functions is still poorly understood. Herein we used in vivo imaging techniques, including confocal microscopy and scintigraphy, to show that vagus nerve stimulation increases the phagocytosis activity by resident macrophages in the liver, even on the absence of an immune challenge. The activation of this neural circuit in a non-lethal model of sepsis optimized the removal of bacteria in the liver and resulted in the production of anti-inflammatory and pro-regenerative cytokines. Our findings provide new insights into the neural regulation of the immune system in the liver.
In spite of therapeutic approaches, liver cancer is still one of the deadliest type of tumor in which tumor microenvironment may play an active role in the outcome of the disease. Decorin, a small leucine-rich proteoglycan is not only responsible for assembly and maintenance of the integrity of the extracellular matrix, but a natural inhibitor of cell surface receptors, thus it exerts antitumorigenic effects. Here we addressed the question whether this effect of decorin is independent of the tumor phenotypes including differentiation, proliferation and invasion.
Chronic low-grade adipose inflammation, characterized by aberrant adipokine production and pro-inflammatory macrophage activation/polarization is associated with increased risk of breast cancer. Adipocyte fatty acid composition is influenced by dietary availability and may regulate adipokine secretion and adipose inflammation. After feeding F344 rats for 20 weeks with a Western diet or a fish oil-supplemented diet, we cultured primary rat adipose tissue in a three-dimensional explant culture and collected the conditioned medium. The rat adipose tissue secretome was assayed using the Proteome Profiler Cytokine XL Array, and adipose tissue macrophage polarization (M1/M2 ratio) was assessed using the iNOS/ARG1 ratio. We then assessed the adipokine's effects upon stem cell self-renewal using primary human mammospheres from normal breast mammoplasty tissue. Adipose from rats fed the fish oil diet had an ω-3:ω-6 fatty acid ratio of 0.28 compared to 0.04 in Western diet rats. The adipokine profile from the fish oil-fed rats was shifted toward adipokines associated with reduced inflammation compared to the rats fed the Western diet. The M1/M2 macrophage ratio decreased by 50% in adipose of fish oil-fed rats compared to that from rats fed the Western diet. Conditioned media from rats fed the high ω-6 Western diet increased stem cell self-renewal by 62%±9% (X¯%±SD) above baseline compared to only an 11%±11% increase with the fish oil rat adipose. Modulating the adipokine secretome with dietary interventions therefore may alter stromal-epithelial signaling that plays a role in controlling mammary stem cell self-renewal.
Patients who sustain a traumatic brain injury (TBI) are known to have a significantly quicker fracture healing time than patients with isolated fractures, but the underlying mechanism has yet to be identified. In this study, we found that the upregulation of miRNA-26a-5p induced by TBI correlated with a decrease in phosphatase and tensin homolog (PTEN) in callus formation. In vitro, overexpressing miRNA-26a-5p inhibited PTEN expression and accelerated osteoblast differentiation, whereas silencing of miRNA-26a-5p inhibited osteoblast activity. Reduction of PTEN facilitated osteoblast differentiation via the PI3K/AKT signaling pathway. Through luciferase assays, we found evidence that PTEN is a miRNA-26a-5p target gene that negatively regulates the differentiation of osteoblasts. Moreover, the present study confirmed that preinjection of agomiR-26a-5p leads to increased bone formation. Collectively, these results indicate that miRNA-26a-5p overexpression may be a key factor governing the improved fracture healing observed in TBI patients after the downregulation of PTEN and PI3K/AKT signaling. Upregulation of miRNA-26a-5p may therefore be a promising therapeutic strategy for promoting fracture healing.
Podosphaera xanthii is the main causal agent of powdery mildew disease in cucurbits and is responsible for important yield losses in these crops worldwide. Powdery mildew fungi are obligate biotrophs. In these parasites, biotrophy is determined by the presence of haustoria, which are specialized structures of parasitism developed by these fungi for the acquisition of nutrients and the delivery of effectors. Detailed molecular studies of powdery mildew haustoria are scarce due mainly to difficulties in their isolation. Therefore, their analysis is considered an important challenge for powdery mildew research. The aim of this work was to gain insights into powdery mildew biology by analysing the haustorial transcriptome of P. xanthii.
The oilseed Camelina sativa is grown for a range of applications, including for biofuel, biolubricants, and as a source of omega-3 fatty acids for the aquaculture feed industry. The seed meal co-product is used as a source of protein for animal feed; however, the low value of the meal hinders profitability and more widespread application of camelina. The nutritional quality of the seed meal is largely determined by the abundance of specific seed storage proteins and their amino acid composition. Manipulation of seed storage proteins has been shown to be an effective means for either adjustment of nutritional content of seeds or for enhancing accumulation of high-value recombinant proteins in seeds.
Breast cancer is the most common cancer diagnosed in women worldwide. In developed countries, 80-90% of women will survive five years after diagnosis but the transition from hospital-based care to health self-management and self-efficacy can be difficult. Text messaging programs offer a simple and proven way to provide support to people with chronic diseases. This study aims to test the effectiveness of a text message support program at improving women's health self-efficacy, and physical and mental health outcomes after breast cancer treatments compared to usual care at 6-months and to understand the barriers and enablers to widespread implementation.
Less than 2% of children in the U.S., ages 9-13, meet the minimum dietary recommendations for vegetable intake. The home setting provides potential opportunities to promote dietary behavior change among children, yet limited trials exist with child vegetable intake as a primary outcome. Strategies to increase vegetable intake grounded in behavioral economics are no/low cost and may be easily implemented in the home by parents.
Non-communicable diseases (NCDs), particularly cardiovascular diseases, diabetes, respiratory conditions and cancers, are the most common causes of morbidity and mortality globally. Information on the prevalence estimates of NCD risk factors such as smoking, low fruit & vegetable intake, physical inactivity, raised blood pressure, overweight, obesity and abnormal blood lipid are scarce in Somaliland. The aim of this study was to determine the prevalence of these selected risk factors for NCDs among 20-69 year old women and men in Hargeisa, Somaliland.
The implementation of interventions at-scale is required to maximise population health benefits. 'Physical Activity 4 Everyone (PA4E1)' was a multi-component school-based program targeting adolescents attending secondary schools in low socio-economic areas. An efficacy trial of the intervention demonstrated an increase in students' mean minutes of moderate-to-vigorous physical activity (MVPA) per day and lower weight gain at low incremental cost. This study aims to assess the effectiveness and cost effectiveness of a multi-component implementation support intervention to improve implementation, at-scale, of the evidence based school physical activity (PA) practices of the PA4E1 program. Impact on student PA levels and adiposity will also be assessed, in addition to the cost of implementation.
Cucurbitacin B is the major bioactive constituent in Trichosanthes cucumerina L. fruits, which the pharmacological properties have been studied for decades particularly an anti-tumor activity. The pharmacokinetic profile of this compound is still limited and investigation is needed for further phytopharmaceutical product development. This study aimed to investigate the pharmacokinetic profile of cucurbitacin B after administering the compound at different doses and routes to rats.
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. It is a disease known worldwide for its vulnerability factors, magnitude and mortality. The objective of the study was to analyze the spatial and temporal dynamics of TB in the area of social inequality in northeast Brazil between the years 2001 and 2016.
The introduction of the new generation of particle-filled and high strength ceramics, hybrid composites and technopolymers in the last decade has offered an extensive palette of dental materials broadening the clinical indications in fixed prosthodontics, in the light of minimally invasive dentistry dictates. Moreover, last years have seen a dramatic increase in the patients' demand for non-metallic materials, sometimes induced by metal-phobia or alleged allergies. Therefore, the attention of scientific research has been progressively focusing on such materials, particularly on lithium disilicate and zirconia, in order to shed light on properties, indications and limitations of the new protagonists of the prosthetic scene.
People who have had anterior cruciate ligament reconstruction (ACLR) are at a high risk of developing tibiofemoral joint (TFJ) osteoarthritis (OA), with concomitant meniscal injury elevating this risk. This study aimed to investigate OA-related morphological change over 2 years in the TFJ among individuals who have undergone ACLR with or without concomitant meniscal pathology and in healthy controls. A secondary aim was to examine associations of baseline TFJ cartilage defects and bone marrow lesions (BML) scores with tibial cartilage volume change in ACLR groups.
Chronic disease is a global concern. While ample research has aimed to identify the epidemiology of multimorbidity and patient complexity using administrative data, little attention has been paid to the processes of care that treating complex patients entail. Consequently, the concept of patient complexity itself does not directly speak to how challenging it may be to care for a given patient. The purpose of this study was to investigate how primary care providers define, encounter, and manage complex patients, especially those with chronic pain. To our knowledge, this is the first study to move beyond general narrative descriptions of complexity towards an interrogation that is grounded in the work practices of caring for these patients.
Localization of small and/or deep pulmonary nodules before thoracoscopic exploration is paramount to minimize the likelihood of unplanned conversion to thoracotomy. As far as the percutaneous approach is concerned, the most common workflow consists of preoperative computed tomography (POCT) imaging-guided tumor marking (performed in an interventional CT suite) followed by their removal in an operating room (OR). However, the advent of hybrid ORs has allowed intraoperative computed tomography (IOCT)-guided lesion localization. This single center, open-label, randomized, controlled clinical trial aims to compare the efficacy and safety of IOCT versus POCT.
Distortion of taste sensations is a common chemotherapy-induced side effect; however, treatment evidence is limited. Pilot data indicated that acupuncture might be able to improve symptoms of dysgeusia. Thus, the aim of this study is to investigate the effects and side effects of hypoglossal acupuncture in the treatment of dysgeusia in patients with breast cancer undergoing chemotherapy.
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