Role of Dendritic Cell in Diabetic Nephropathy Kim, Hyunwoo; Kim, Miyeon; Lee, Hwa-Young ...
International journal of molecular sciences,
07/2021, Letnik:
22, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Diabetic nephropathy (DN) is one of the most significant microvascular complications in diabetic patients. DN is the leading cause of end-stage renal disease, accounting for approximately 50% of ...incident cases. The current treatment options, such as optimal control of hyperglycemia and elevated blood pressure, are insufficient to prevent its progression. DN has been considered as a nonimmune, metabolic, or hemodynamic glomerular disease initiated by hyperglycemia. However, recent studies suggest that DN is an inflammatory disease, and immune cells related with innate and adaptive immunity, such as macrophage and T cells, might be involved in its development and progression. Although it has been revealed that kidney dendritic cells (DCs) accumulation in the renal tissue of human and animal models of DN require activated T cells in the kidney disease, little is known about the function of DCs in DN. In this review, we describe kidney DCs and their subsets, and the role in the pathogenesis of DN. We also suggest how to improve the kidney outcomes by modulating kidney DCs optimally in the patients with DN.
AMP-activated protein kinase (AMPK) plays a key role in controlling energy metabolism in response to physiological and nutritional status. Although AMPK activation has been proposed as a promising ...molecular target for treating obesity and its related comorbidities, the use of pharmacological AMPK activators has been met with contradictory therapeutic challenges. Here we show a regulatory mechanism for AMPK through its ubiquitination and degradation by the E3 ubiquitin ligase makorin ring finger protein 1 (MKRN1). MKRN1 depletion promotes glucose consumption and suppresses lipid accumulation due to AMPK stabilisation and activation. Accordingly, MKRN1-null mice show chronic AMPK activation in both liver and adipose tissue, resulting in significant suppression of diet-induced metabolic syndrome. We demonstrate also its therapeutic effect by administering shRNA targeting MKRN1 into obese mice that reverses non-alcoholic fatty liver disease. We suggest that ubiquitin-dependent AMPK degradation represents a target therapeutic strategy for metabolic disorders.
PurposeThe National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) is a cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of ...Korea. The NHIS constructed the NHIS-HEALS cohort database in 2015. The purpose of this cohort is to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker.ParticipantsTo construct the NHIS-HEALS database, a sample cohort was first selected from the 2002 and 2003 health screening participants, who were aged between 40 and 79 in 2002 and followed up through 2013. This cohort included 514 866 health screening participants who comprised a random selection of 10% of all health screening participants in 2002 and 2003.Findings to dateThe age-standardised prevalence of anaemia, diabetes mellitus, hypertension, obesity, hypercholesterolaemia and abnormal urine protein were 9.8%, 8.2%, 35.6%, 2.7%, 14.2% and 2.0%, respectively. The age-standardised mortality rate for the first 2 years (through 2004) was 442.0 per 100 000 person-years, while the rate for 10 years (through 2012) was 865.9 per 100 000 person-years. The most common cause of death was malignant neoplasm in both sexes (364.1 per 100 000 person-years for men, 128.3 per 100 000 person-years for women).Future plansThis database can be used to study the risk factors of non-communicable diseases and dental health problems, which are important health issues that have not yet been fully investigated. The cohort will be maintained and continuously updated by the NHIS.
In mammalian cells, nearly one-third of proteins are inserted into the endoplasmic reticulum (ER), where they undergo oxidative folding and chaperoning assisted by approximately 20 members of the ...protein disulfide isomerase family (PDIs). PDIs consist of multiple thioredoxin-like domains and recognize a wide variety of proteins via highly conserved interdomain flexibility. Although PDIs have been studied intensely for almost 50 years, exactly how they maintain protein homeostasis in the ER remains unknown, and is important not only for fundamental biological understanding but also for protein misfolding- and aggregation-related pathophysiology. Herein, we review recent advances in structural biology and biophysical approaches that explore the underlying mechanism by which PDIs fulfil their distinct functions to promote productive protein folding and scavenge misfolded proteins in the ER, the primary factory for efficient production of the secretome.
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•Oxidative folding and chaperoning in the ER are assisted by ~20 PDI family members.•PDIs recognize and act on clients via conserved interdomain flexibility.•Exactly how PDIs maintain protein homeostasis remains to be uncovered.•Aberrant PDI activity leads to protein misfolding- and aggregation-related pathology.
(L.) Cusson, a member of the
family, is rich in coumarins, such as imperatorin and osthole.
fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and ...sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1-30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca
-activated K
channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl
. The main active compounds of CM, i.e., imperatorin (3-300 µM) and osthole (1-100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential.
Metal nanoparticle surfaces are used for peroxidase‐ and oxidase‐like nanozymes but not for esterase‐like nanozymes. It is challenging to obtain rapid catalytic hydrolysis on a metal surface and even ...more so without a catalytically labile substrate. Here, we report that metal nanoparticle surfaces rapidly catalyze non‐redox ester hydrolysis in the presence of redox H3N−BH3 (AB). Metal hydrides are readily generated on a Pt nanoparticle (PtNP) from AB, and as a result the PtNP becomes electron‐rich, which might assist nucleophilic attack of H2O on the carbonyl group of an ester. The nanozyme system based on PtNP, AB, and 4‐aminonaphthalene‐1‐yl acetate provides an electrochemical signal‐to‐background ratio much higher than natural enzymes, due to the rapid ester hydrolysis and redox cycling involving the hydrolysis product. The nanozyme system is applied in a sensitive electrochemical immunosensor for thyroid‐stimulating hormone detection. The calculated detection limit is approximately 0.3 pg mL−1, which indicates the high sensitivity of the immunosensor using the PtNP nanozyme.
Metal nanoparticle surfaces rapidly catalyze non‐redox ester hydrolysis in the presence of redox H3N−BH3. Metal hydrides on a Pt nanoparticle might assist nucleophilic attack of H2O on the carbonyl group of an ester. The ester hydrolysis is applied in a sensitive electrochemical immunosensor for thyroid‐stimulating hormone detection.
The incidence of venous thromboembolism (VTE) is lower in Asian populations than in Western populations. The objective of the present study was to evaluate the annual age- and sex-adjusted incidence ...(ASR) of VTE from 2009 to 2013 in South Korea. In addition, annual change in the pattern of VTE treatment during the study period was estimated because a new direct oral anticoagulant (DOAC) had become available and was covered by health insurance in Korea beginning in January 2013. VTE cases from 2009 to 2013 were retrospectively identified based on both diagnostic and medication codes of anticoagulants used for initial treatment using the Korean Health Insurance Review and Assessment Service (HIRA) databases. The incidence of VTE increased yearly. It was significantly higher in the older population than in the younger population, and it was higher in females than in males. In 2009, ASRs of VTE, deep vein thrombosis, and pulmonary embolism were 21.3, 8.1, and 13.2 cases per 100,000 individuals, respectively in 2009. These increased to 29.2, 12.7, and 16.6 cases per 100,000, respectively, in 2013. Prescription rates of warfarin and low-molecular-weight heparin decreased with the introduction of a new anticoagulant in 2013. The proportion of subjects who underwent mechanical procedures decreased annually. The ASR of VTE in Korea continuously increased from 2009 to 2013, reflecting an increased awareness and detection of VTE as well as improved survival of patients with cancer and other morbidities. Following its introduction, DOAC rapidly replaced other anticoagulants for the treatment of VTE.
Carbon monoxide (CO) is recently accepted as a therapeutic molecule that exhibits remarkable biological actions, including anti‐inflammation, antiapoptosis, and cytoprotection, at a physiological ...level. For clinical use without the side effect of tissue hypoxia, which arises from the uncontrolled administration of CO in the human body, CO‐releasing molecules (CORMs) are developed to ensure safe and efficient CO‐delivery. Herein, a syringe‐injectable CO‐releasing peptide hydrogel (COH) and a corresponding bioadhesive hydrogel patch (COHP), developed by rational supramolecular chemistry, to enhance the therapeutic efficacy of CO with controllable CO‐release to a specific tissue is report. The injectable COH is prepared by self‐assembly of the CORM‐attached peptides with a gel‐forming diphenylalanine‐derivative, resulting in fibrillar networks and exhibiting prolonged CO‐release compared with CORMs. Furthermore, Ca2+‐chelating and mussel‐derived catechol‐functionalized peptides are introduced to afford a mechanically rigid, bioadhesive COHP that elicits cytoprotective and anti‐inflammatory activities. The supramolecular COHP can be utilized in the efficient CO‐delivery to the site of interest by conformal contacts, making it a promising scaffold for biomedical applications.
A therapeutic carbon monoxide (CO)‐releasing hydrogel patch is fabricated by self‐assembly of rationally designed peptides. Increase in mechanical strength and adhesive force of hydrogel enables the local CO‐delivery with its sustained release. The hydrogel patch elicits effective cytoprotective and anti‐inflammatory effects on cardiomyocytes by conformally contacting with the desired tissues, resulting in an efficient nanoplatform for a medical gas therapy.
For the effective application of surface‐enhanced Raman scattering (SERS) nanoprobes for in vivo targeting, the tissue transparency of the probe signals should be as high as it can be in order to ...increase detection sensitivity and signal reproducibility. Here, near‐infrared (NIR)‐sensitive SERS nanoprobes (NIR SERS dots) are demonstrated for in vivo multiplex detection. The NIR SERS dots consist of plasmonic Au/Ag hollow‐shell (HS) assemblies on the surface of silica nanospheres and simple aromatic Raman labels. The diameter of the HS interior is adjusted from 3 to 11 nm by varying the amount of Au3+ added, which results in a red‐shift of the plasmonic extinction of the Au/Ag nanoparticles toward the NIR (700–900 nm). The red‐shifted plasmonic extinction of NIR SERS dots causes enhanced SERS signals in the NIR optical window where endogenous tissue absorption coefficients are more than two orders of magnitude lower than those for ultraviolet and visible light. The signals from NIR SERS dots are detectable from 8‐mm deep in animal tissues. Three kinds of NIR SERS dots, which are injected into live animal tissues, produce strong SERS signals from deep tissues without spectral overlap, demonstrating their potential for in vivo multiplex detection of specific target molecules.
Near‐infrared‐sensitive surface‐enhanced Raman scattering nanoprobes (NIR SERS dots) are fabricated by forming plasmonic Au/Ag hollow‐shells, which assemble on silica nanospheres. A single NIR SERS dot is capable of generating a strong SERS signal (average SERS enhancement factor value 2.8 × 105) with high reproducibility. In addition, the signals from NIR SERS dots are effectively detected from deep tissues of up to 8 mm depth and have exhibited a capability for in vivo multiplex detection in a live animal study.
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