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Pathophysiological and also Pharmacological Traits involving KCNJ5 157-159delITE Somatic Mutation inside Aldosterone-Producing Adenomas.
On one hand, IR820@ZIF-8 is modified with hyaluronic acid for realizing tumor-targeted photothermal therapy, accompanied with the release of tumor antigens. On the other hand, (R837+1 MT)@ZIF-8 is modified with mannan for achieving DCs-targeted immune amplification. The synergistic tumor cells-targeted treatment and DCs-targeted immunomodulation can efficiently overcome two major obstacles in immunotherapy inadequate activation of immune response and immune evasion, offering powerful platform against invasive malignancy and rechallenged tumors. It is difficult to carry out early diagnosis and treatment of Multiple sclerosis (MS) because of the complex pathogenesis elicited by diversified autoantigens. Monocytes play important roles in the process of MS, especially as most of the amplified inflammatory monocytes cross the BBB to promote neuron injury and recruit more immune cells to infiltrate the central nervous system (CNS). Here, we propose monocytes as an effective immunotherapy target for MS. We used High-density lipoprotein-mimicking peptide-phospholipid scaffold (HPPS) as a carrier to improve the bioavailability of curcumin. Curcumin-loaded HPPS (Cur-HPPS) were taken up specifically and efficiently by monocytes through the scavenger receptor class B type I (SR-B1) receptor. This delivery hindered inflammatory monocytes across the BBB in EAE mice, inhibited the proliferation of microglia, and restricted the infiltration of other effector immune cells, resulting in the reduction of EAE morbidity from 100% to 30%. It attributed to the immunomodulatory effect of Cur-HPPS on inflammatory monocytes, which inhibited NF-κB activation and downregulated the expression of adhesion-and migration-related molecules. Meanwhile, infiltrated monocytes in the CNS of EAE mice characterize early inflammation. Therefore, targeted modulation of monocytes with HPPS carrying therapeutic and/or imaging agents offers a novel strategy for MS diagnosis and treatment. Diabetes is an increasing health problem and associated with inflammatory complications that seriously affects the quality of life and survival of patients. Carbon monoxide (CO), owing to its anti-inflammatory and anti-apoptotic properties, has become a potential therapeutic molecule for the treatment of autoimmune diseases. Here, we constructed a mesoporous silica-based biomimetic CO nanogenerator (mMMn), which was loaded with manganese carbonyl and camouflaged with macrophage membrane. Driven by the active targeting of macrophage membrane to inflammatory sites, the as-designed mMMn could effectively accumulate in pancreatic tissue of type 1 diabetic mice, which was established by consecutive administration of streptozotocin (STZ). It was found that the local reactive oxygen species (ROS) within pancreas could trigger the continuous CO release from mMMn, which greatly ameliorated diabetes in mice with improved blood glucose homeostasis by alleviating inflammatory responses and inhibiting β-cells apoptosis. The exogenous CO targeting to pancreatic tissue paves a novel way for the treatment of type 1 diabetes. Ex-vivo blood-brain barrier (BBB) model is of great value for studying brain function and drug development, but it is still challenging to engineer macroscale three-dimensional (3D) tissue constructs to recapitulate physiological and functional aspects of BBB. Here, we describe a delicate 3D vascularized neural constructs for ex-vivo reconstitution of BBB function. The tissue-engineered tissue construct is based on a multicomponent 3D co-culture of four types of cells, which typically exist in the BBB and were spatially defined and organized to mimic the in vivo BBB structure and function. A porous polycaprolactone/poly (d,l-lactide-co-glycolide) (PCL/PLGA) microfluidic perfusion system works as the vasculature network, which was made by freeze-coating a 3D-printed sacrificial template. Endothelial cells were seeded inside the channels of the network to form 3D interconnected blood vessels; while other types of cells, including pericytes, astrocytes, and neurons, were co-cultured in a collagen matrix wrapping the vasculature network to derive a vascularized neural construct that recapitulates in vivo BBB function with great complexity and delicacy. Using this model, we successfully reconstituted BBB function with parameters that are similar to the in vivo condition, and demonstrated the identification of BBB-penetrating therapeutics by examining the molecular delivery to neuronal cells when relevant biologic molecules were applied to the vasculature circulation system of the neural construct. Saponins are amphiphilic glycosidic secondary metabolites produced by numerous plants. So far only few of them have been thoroughly analyzed and even less have found industrial applications as biosurfactants. In this contribution we screen 45 plants from different families, reported to be rich in saponins, for their surface activity and foaming properties. For this purpose, the room-temperature aqueous extracts (macerates) from the alleged saponin-rich plant organs were prepared and spray-dried under the same conditions, in presence of sodium benzoate and potassium sorbate as preservatives and drying aids. For 15 selected plants, the extraction was also performed using hot water (decoction for 15 min) but high temperature in most cases deteriorated surface activity of the extracts. To our knowledge, for most of the extracts this is the first quantitative report on their surface activity. BIX 01294 price Among the tested plants, only 3 showed the ability to reduce surface tension of their solutions by more than 20 mN/m at 1% oposed as the best potential sources of saponins for surfactant applications in natural cosmetic and household products. V.T-2 toxin is a kind of group A trichothecenes mycotoxins, frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK, Glut2, Fas, Acox1, Hmgcr, PPARα, Srebp1 and CD36.
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