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Hesselberg Berger posted an update 3 days, 4 hours ago
The imbalance of amyloid-β (Aβ) production and clearance causes aggregation of Aβ1-42 monomers to form fibrils and amyloid plaques, which is an indispensable process in the pathogenesis of Alzheimer’s disease (AD), and eventually leads to pathological changes and cognitive impairment. Consequently, Aβ1-42 is the most important target for the treatment of AD. However, developing a single treatment method that can recognize Aβ1-42 , inhibit Aβ1-42 fibrillation, eliminate amyloid plaques, improve cognitive impairments, and alleviate AD-like pathology is challenging. Here, a coassembly composed of cyclodextrin (CD) and calixarene (CA) is designed, and it is used as an anti-Aβ therapy agent. The CD-CA coassembly is based on the previously reported heteromultivalent recognition strategy and is able to successfully eliminate amyloid plaques and degrade Aβ1-42 monomers in 5xFAD mice. More importantly, the coassembly improves recognition and spatial cognition deficits, and synaptic plasticity impairment in the 5xFAD mice. In addition, the coassembly ameliorates AD-like pathology including prevention of neuronal apoptosis and oxidant stress, and alteration of M1/M2 microglial polarization states. This supramolecular approach makes full use of both molecular recognition and self-assembly of macrocyclic amphiphiles, and is a promising novel strategy for AD treatment.Astragalus L. is widely distributed throughout the temperate regions of Europe, Asia, and North America. The genus is widely used in folk medicine and in dietary supplements, as well as in cosmetics, teas, coffee, vegetable gums, and as forage for animals. The major phytoconstituents of Astragalus species with beneficial properties are saponins, flavonoids, and polysaccharides. Astragalus extracts and their isolated components exhibited promising in vitro and in vivo biological activities, including antiaging, antiinfective, cytoprotective, antiinflammatory, antioxidant, antitumor, antidiabesity, and immune-enhancing properties. Considering their proven therapeutic potential, the aim of this work is to give a comprehensive summary of the Astragalus spp. and their active components, in an attempt to provide new insight for further clinical development of these xenobiotics. This is the first review that briefly describes their ethnopharmacology, composition, biological, and toxicological properties.Immunotherapy has offered new treatment options for cancer; however, the therapeutic benefits are often modest and desired to be improved. A semiconducting polymer nanoadjuvant (SPNII R) with a photothermally triggered cargo release for second near-infrared (NIR-II) photothermal immunotherapy is reported here. SPNII R consists of a semiconducting polymer nanoparticle core as an NIR-II photothermal converter, which is doped with a toll-like receptor (TLR) agonist as an immunotherapy adjuvant and coated with a thermally responsive lipid shell. Upon NIR-II photoirradiation, SPNII R effectively generates heat not only to ablate tumors and induce immunogenic cell death (ICD), but also to melt the lipid layers for on-demand release of the TLR agonist. The combination of ICD and activation of TLR7/TLR8 enhances the maturation of dendritic cells, which amplifies anti-tumor immune responses. Thus, a single treatment of SPNII R-mediated NIR-II photothermal immunotherapy effectively inhibits growth of both primary and distant tumors and eliminates lung metastasis in a murine mouse model. This study thus provides a remote-controlled smart delivery system to synergize photomedicine with immunotherapy for enhanced cancer treatment.Spontaneous emphysematous splenitis is a life-threatening condition reported rarely in humans; however, published reports in dogs are currently lacking. The aim of this multicentric, retrospective, case series design study was to describe radiographic and ultrasonographic imaging findings in Golden Retriever dogs diagnosed with spontaneous emphysematous splenitis. Mitoquinone molecular weight A total of three dogs were sampled. All dogs had a history of lethargy, diarrhea, and weight loss. Radiographic findings in all dogs included a mass effect with focal or multifocal coalescing “vesicular-like” gas pattern in the splenic region and focal loss of serosal detail. Ultrasonographic findings in all dogs included focal or multifocal irregularly shaped, hypoechoic areas containing a mixture of hyperechoic fluid and gas within the splenic parenchyma, hyperechoic abdominal free fluid, and generalized hyperechoic mesenteric fat without evidence of splenic torsion. Pneumoperitoneum was detected ultrasonographically and radiographically in two dogs. All three dogs underwent splenectomy and splenic torsion was definitively ruled out at surgery. One dog died three days after surgery, whereas the other two dogs recovered uneventfully. Culture of the splenic tissue and free abdominal fluid was positive for Clostridium spp. in all three cases. Findings supported inclusion of spontaneous emphysematous splenitis and septic peritonitis as differential diagnoses for dogs with this combination of clinical and imaging characteristics.
A subset of patients with hypertrophic cardiomyopathy (HCM) is at high risk of sudden cardiac death (SCD). Practice guidelines endorse use of a risk calculator, which requires entry of left atrial (LA) diameter. However, American Society of Echocardiography (ASE) guidelines recommend the use of LA volume index (LAVI) for routine quantification of LA size. The aims of this study were to (a) develop a model to estimate LA diameter from LAVI and (b) evaluate whether substitution of measured LA diameter by estimated LA diameter derived from LAVI reclassifies HCM-SCD risk.
The study cohort was comprised of 500 randomly selected HCM patients who underwent transthoracic echocardiography (TTE). LA diameter and LAVI were measured offline using digital clips from TTE. Linear regression models were developed to estimate LA diameter from LAVI. A European Society of Cardiology endorsed equation estimated SCD risk, which was measured using LA diameter and estimated LA diameter derived from LAVI.
The mean LAVI was 48.