The activities of daily living (ADL) ability level of an elderly patient is an important indicator in determining the patient’s degree of degenerative brain disease and is mainly evaluated through ...face-to-face interviews with doctors and patients in hospitals. It is impossible to determine the exact ADL ability of a patient through such a temporary interview, and the pursuit of accurate ADL ability evaluation technology is a very important research task worldwide. In this paper, in order to overcome the limitations of the existing ADL evaluation method mentioned above, first of all, a self-organized IoT architecture in which IoT devices autonomously and non-invasively measure a patient’s ADL ability within the context of the patient’s daily living place was designed and implemented. Second, a remote rehabilitation treatment concept for enhancing the patient’s ADL ability we call an “e-coaching framework”, in which a doctor remotely gives an instruction in a specific ADL scenario, and the patient’s ability to understand and perform the instruction can be measured on-line and in real time, was additionally developed on top of the self-organized IoT architecture. In order to verify the possibility of remote rehabilitation treatment through the proposed architecture, various remotely directed ADL scenarios were performed and the accuracy of the measurements was verified.
Targeted therapy based on protein–drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein ...binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C‐terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR‐specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody–drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody–drug conjugates in human plasma, negligible off‐target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy.
A chemoenzymatic conjugation method that is based on enzymatic prenylation and oxime ligation is a simple and efficient means for generating highly stable and homogeneous protein–drug conjugates in a site‐specific manner. It can be generally applied to the conjugation of drugs to a wide range of protein binders, facilitating the development of targeted therapies with high efficacies and low off‐target effects.
Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier ...integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.
Abstract
Aims
Oral health problems such as periodontal disease, dental caries, and tooth loss have been suggested to have associations with cardiovascular disease. This study aimed to evaluate ...whether oral hygiene behaviour can alleviate cardiovascular risk associated with oral health status using a nationwide population-based cohort.
Methods and results
The data of 247 696 healthy adults aged 40 years or older who underwent an oral health screening programme and had no history of major cardiovascular events were extracted from the National Health Insurance System-National Health Screening Cohort. After a median follow-up of 9.5 years, 14 893 major cardiovascular events occurred including cardiac death, myocardial infarction, stroke, and heart failure. The risk of cardiovascular events was higher when a subject had periodontal disease, a higher number of dental caries, or more tooth loss. Performing one more tooth brushing a day was associated with a 9% significantly lower risk of cardiovascular events after multivariable adjustment. Regular dental visits (once a year or more) for professional cleaning were also shown to reduce cardiovascular risk by 14%. Improved oral hygiene behaviours were shown to attenuate the cardiovascular risk originating from periodontal disease, dental caries, and tooth loss.
Conclusion
Oral hygiene care such as frequent tooth brushing and regular dental visits for professional cleaning reduced the risk of future cardiovascular events in healthy adults. This study also suggests that improved oral hygiene behaviour may modify the association between oral health and cardiovascular diseases.
Aim
To evaluate the effect of dental screening on the risk of cardiovascular disease (CVD) using data from a nationwide population‐based cohort.
Materials and Methods
This retrospective cohort study ...extracted data of 478,245 individuals aged 40–79 years who participated in a health screening programme during 2002–2003 from the National Health Insurance Service–National Health Screening Cohort. Based on screening experience, participants were classified into the non‐screening, general screening only, and dental screening groups. Using Cox proportional hazard models, hazard ratios (HRs) were determined for major adverse cardiovascular events (MACE) during each group's 11‐year follow‐up period.
Results
The risk of MACE in the dental screening group was 10% lower than that in the non‐screening group (adjusted HR, 0.90; 95% confidence interval CI, 0.87–0.93; p < .001) and 9% lower than that in the general screening only group (adjusted HR, 0.91; 95% CI, 0.89–0.94; p < .001).
Conclusions
Dental screening was associated with a lower MACE risk; however, decreases in CVD‐related healthcare utilization and costs were not clinically significant. The association could be attributed to healthy habits of participants in the dental screening group; nevertheless, it is conceivable that the improvement of oral health through dental screening influenced CVD prevention.
Background
Gastric cancer (GC) is a common malignancy worldwide, with a major attribution to
Helicobacter pylori
. Interleukin (IL)-17A has been reported to be up-regulated in serum and tumor of GC ...patients, but the precise mechanisms underlying its involvement in gastric tumorigenesis are yet to be established. Here, we investigated the roles of IL-17A in the pathogenesis of
H. pylori
-induced GC.
Methods
GC was induced in IL-17A knockout (KO) and wild-type (WT) mice via
N
-methyl-
N
-nitrosourea (MNU) treatment and
H. pylori
infection. At 50 weeks after treatment, gastric tissues were examined by histopathology, immunohistochemistry, and immunoblot analyses. In vitro experiments on the human GC cell lines were additionally performed to elucidate the underlying mechanisms.
Results
Deletion of IL-17A suppressed MNU and
H. pylori
-induced gastric tumor development accompanied by a decrease in gastric epithelial cell growth, oxidative stress, and expression of gastric epithelial stem cells markers. In AGS cells, recombinant human IL-17A (rhIL-17A) inhibited apoptosis and G1/S phase transition arrest while promoting reactive oxygen species production, sphere formation ability of cancer stem cells (CSC), and expression of stemness-related genes. In addition, rhIL-17A induced expression of IL-17RC, leading to NF-κB activation and increased NADPH oxidase 1 (NOX1) levels. Inhibition of NOX1 with GKT136901 attenuated rhIL-17A-mediated elevation of GC cell growth, ROS generation, and CSC stemness. Clinically, IL-17RC expressions were significantly upregulated in human GC compared with normal gastric tissues.
Conclusion
Our results suggest that IL-17A promotes gastric carcinogenesis, in part, by regulating IL-17RC/NF-κB/NOX1 pathway, supporting its potential as a target in human GC therapy.
As agonists of TLR7/8, single‐stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off‐target effects or innate immune overactivation. However, low stability prevents them from ...mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA‐based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA‐O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen‐presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA‐O may increase the efficacy of ssRNA‐based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.
An ssRNA adjuvant formulated with coordinative amphiphiles, bearing a zinc/dipicolylamine complex moiety (Zn/DPA) as a coordinative phosphate binder, promoted effective recognition and antigen‐presenting cell (APC) activation. NP=nanoparticle.
Pirfenidone (PRF) is an anti-fibrotic agent that has been approved by the Food and Drug Administration (FDA) for the treatment of mild to moderate idiopathic pulmonary fibrosis. However, the current ...oral administration dosing regimen of PRF is complex and requires high doses. Patients are instructed to take PRF three times daily, with each dose consisting of up to three capsules or tablets (600 mg/d or 1.8 g/d of PRF) taken with food. To improve the dosing regimen, efforts are being made to develop an extended-release tablet with a zero-order release pattern. In this study, two types of extended-release matrix tablets were compared: non-channeled extended-release matrix tablets (NChMT) and channeled extended-release matrix tablets (ChMT). In vitro release tests, swelling and erosion index, rheology studies, and X-ray microcomputed tomography (XRCT), were conducted. The results indicated that ChMT maintained a zero-order release pattern with a constant release rate, while NChMT exhibited a decreased release rate in the latter half of the dissolution. ChMT exhibited accelerated swelling and erosion compared to other formulations, and this was made possible by the presence of channels within the tablet. These channels allowed for thorough wetting and swelling throughout the entire depth of the tablet. The formation of channels was confirmed through XRCT images. In conclusion, the presence of channels in ChMT tablets increased the rate of swelling and erosion, resulting in a zero-order release pattern. This development offers the potential to improve the dosage of PRF and reduce its associated side effects.
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