Acute kidney injury (AKI)––the sudden loss of kidney function due to tissue damage and subsequent progression to chronic kidney disease––has high morbidity and mortality rates and is a serious ...worldwide clinical problem. Current AKI diagnosis, which relies on measuring serum creatinine levels and urine output, cannot sensitively and promptly report on the state of damage. To address the shortcomings of these traditional diagnosis tools, several molecular biomarkers have been developed to facilitate the identification and ensuing monitoring of AKI. Nanosized membrane-bound extracellular vesicles (EVs) in body fluids have emerged as excellent sources for discovering such biomarkers. Besides this diagnostic purpose, EVs are also being extensively exploited to deliver therapeutic macromolecules to damaged kidney cells to ameliorate AKI. Consequently, many successful AKI biomarker findings and therapeutic applications based on EVs have been made. Here, we review our understanding of how EVs can help with the early identification and accurate monitoring of AKI and be used therapeutically. We will further discuss where current EV-based AKI diagnosis and therapeutic applications fall short and where future innovations could lead us.
Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and ...clopidogrel monotherapy in this population.
We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6–18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.
Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 49·8%) or to the aspirin group (2728 50·2%). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 95% CI 0·59–0·90; p=0·0035).
Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.
ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.
Though emerging evidence indicates that the pathogenesis of Parkinson's disease is strongly correlated to the accumulation
and transmission
of α-synuclein (α-syn) aggregates in the midbrain, no ...anti-aggregation agents have been successful at treating the disease in the clinic. Here, we show that graphene quantum dots (GQDs) inhibit fibrillization of α-syn and interact directly with mature fibrils, triggering their disaggregation. Moreover, GQDs can rescue neuronal death and synaptic loss, reduce Lewy body and Lewy neurite formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of α-syn pathology provoked by α-syn preformed fibrils
. We observe, in vivo, that GQDs penetrate the blood-brain barrier and protect against dopamine neuron loss induced by α-syn preformed fibrils, Lewy body/Lewy neurite pathology and behavioural deficits.
Earthquakes have the greatest destructive effect among all natural disasters. Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and anxiety disorder (AD) are major psychiatric ...disorders (MPD) that can be triggered by exposure to earthquakes. Conventional treatments such as pharmacological treatments have several limitations. Acupuncture therapy as a complementary integrative medicine may be an effective alternative treatment for these limitations. This study aimed to identify the status of the clinical evidence regarding acupuncture therapy for earthquake survivors with MPD. We will follow the scoping review process as previously described. The study question is as follows: "Which types of clinical research designs, study types, study durations, adverse events, and clinical outcomes have been reported regarding acupuncture therapy for MPD in earthquake survivors?" Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, PsycArticles databases, and Chinese, Korean, and Japanese databases will be comprehensively searched electronically from their inception to November 2022. Data from the included studies will be collected and descriptively analyzed in relation to our research question. We will collate, synthesize, and summarize the extracted data according to the analytical framework of a scoping review. The protocol will conform with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensions of Scoping Reviews to ensure the clarity and completeness of our reporting in the whole phase of the scoping review (Protocol registration: https://osf.io/wfru7/). The findings of this scoping review will provide fundamental data that will help researchers identify appropriate research questions and design further studies on the use of acupuncture for MPD management in earthquake survivors. These results will be helpful for developing disaster site-specific research protocols for future clinical trials on this topic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This scoping review aimed to determine the current research status of acupuncture for major psychiatric disorder (MPD) in earthquake survivors.
We followed the scoping review process described ...previously. A literature search on 14 electronic databases was conducted from inception to November 29, 2022. Data from the included studies were collected and descriptively analyzed to address our research question. Extracted data were collated, synthesized, and summarized the according to the analytical framework of a scoping review.
This scoping review included nine clinical studies: four randomized controlled trials (RCTs) and five before-after studies. The most frequent MPD type among the included acupuncture studies was posttraumatic stress disorder (PTSD; 6/9, 66.67%). The most frequent acupuncture type was scalp electro-acupuncture (4/9, 44.44%), followed by manual acupuncture and ear acupressure/ear acupuncture (3/9, 33.33%). Studies using scalp electro-acupuncture all used common acupoints, including GB20, GV20, GV24, and EX-HN1. In general, the treatment period lasted between 4 and 12 weeks. Validated assessment tools for PTSD severity and accompanying symptoms were used for patients with PTSD, while the corresponding evaluation tools were used for patients with other diagnoses or clinical symptoms. Acupuncture-related adverse events were generally mild and temporary, such as mild bleeding and hematoma, and syncope was a rare but potentially serious adverse event (1/48 patients and 1/864 sessions over a treatment period of 4 weeks).
Acupuncture studies for MPD after an earthquake mainly focused on PTSD. RCTs accounted for around half of the included studies. Scalp electro-acupuncture was the most common acupuncture type, and EX-HN1 and GV24 were the most important acupoints in the acupuncture procedures for MPD. The included studies mostly used validated symptom assessment tools, though some did not. Clinical studies in this field need to be further expanded regardless of the study type.
https://osf.io/wfru7/.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Because exosomes have gained attention as a source of biomarkers, we investigated if miRNAs in exosomes (exo-miRs) can report the disease progression of organ injury. Using rat renal ...ischemia-reperfusion injury (IRI) as a model of acute kidney injury (AKI), we determined temporally-released exo-miRs in urine during IRI and found that these exo-miRs could reliably mirror the progression of AKI. From the longitudinal measurements of miRNA expression in kidney and urine, we found that release of exo- miRs was a regulated sorting process. In the injury state, miR-16, miR-24, and miR-200c were increased in the urine. Interestingly, expression of target mRNAs of these exo-miRs was significantly altered in renal medulla. Next, in the early recovery state, exo-miRs (miR-9a, miR-141, miR-200a, miR-200c, miR-429), which share Zeb1/2 as a common target mRNA, were upregulated together, indicating that they reflect TGF-β-associated renal fibrosis. Finally, release of exo-miRs (miR-125a, miR-351) was regulated by TGF-β1 and was able to differentiate the sham and IRI even after the injured kidneys were recovered. Altogether, these data indicate that exo-miRs released in renal IRI are associated with TGF-β signaling. Temporal release of exo-miRs which share targets might be a regulatory mechanism to control the progression of AKI.
Summary
Gene expression is dynamically regulated in a variety of mammalian physiologies. During mammalian aging, there are changes that occur in protein expression that are highly controlled by the ...regulatory steps in transcription, post‐transcription, and post‐translation. Although there are global profiles of human transcripts during the aging processes available, the mechanism(s) by which transcripts are differentially expressed between young and old cohorts remains unclear. Here, we report on N6‐methyladenosine (m6A) RNA modification profiles of human peripheral blood mononuclear cells (PBMCs) from young and old cohorts. An m6A RNA profile identified a decrease in overall RNA methylation during the aging process as well as the predominant modification on proteincoding mRNAs. The m6A‐modified transcripts tend to be more highly expressed than nonmodified ones. Among the many methylated mRNAs, those of DROSHA and AGO2 were heavily methylated in young PBMCs which coincided with a decreased steady‐state level of AGO2 mRNA in the old PBMC cohort. Similarly, downregulation of AGO2 in proliferating human diploid fibroblasts (HDFs) also correlated with a decrease in AGO2 mRNA modifications and steady‐state levels. In addition, the overexpression of RNA methyltransferases stabilized AGO2 mRNA but not DROSHA and DICER1 mRNA in HDFs. Moreover, the abundance of miRNAs also changed in the young and old PBMCs which are possibly due to a correlation with AGO2 expression as observed in AGO2‐depleted HDFs. Taken together, we uncovered the role of mRNA methylation on the abundance of AGO2 mRNA resulting in the repression of miRNA expression during the process of human aging.
Topology control of polymers is critical for determining their physical properties and potential applications; in particular, topologies that incorporate numerous hydrogen bonding (H‐bonding) donors ...and acceptors along the polymer chains considerably influence the formation of different inter‐ and intramolecular H‐bonding motifs. In this study, the high‐level control of inter‐ and intramolecular H‐bonding is investigated in topology‐controlled poly(glycidoxy carbonyl benzoic acid)s (PGCs). Three types of topology‐controlled PGCs (i.e., linear, hyperbranched, and branched cyclic structures having a similar degree of polymerization) are prepared by introducing aromatic carboxylic acids into the corresponding polyglycidols (PGs) via quantitative post‐polymerization modification with phthalic anhydride. The obtained three types of PGCs demonstrated the high‐level interplay between the inter‐ and intramolecular H‐bonding in polymer chains by exhibiting the pH‐dependent self‐association properties in the solution state and the strong adhesion properties in the bulk state with high transparency. Interestingly, the dramatically enhanced adhesive property by 2.6‐fold is demonstrated by simple mixing of branched cyclic PGC and topology‐controlled PGs to promote the cooperative H‐bonding between polymer chains. The new class of cooperative H‐bonding is anticipated between topology‐controlled polymers to contribute to the development of advanced adhesive and the high potential in biological and biomedical applications due to its excellent biocompatibility.
A dramatic enhancement of the adhesion performance is obtained via cooperative H‐bonding between a simple mixture of a branched cyclic poly(glycidoxy carbonyl benzoic acid) (PGC) with a linear polyglycidol. The resulting adhesive is capable of resisting a 30 kg load repeatedly without failure. Additionally, the synthesized PGCs exhibit excellent biocompatibility with living cells, thus indicating the potential of these adhesives for use in biological and biomedical applications.
Posttraumatic stress disorder is caused by traumatic events such as death, serious injury, and sexual violence. Military personnel and veterans are at high risk for posttraumatic stress disorder. ...Conventional posttraumatic stress disorder treatments have certain limitations. Complementary and integrative medicine treatments, especially acupuncture, are potential novel first-line treatments that may overcome these limitations. We aim to investigate the current status of the available clinical evidence related to acupuncture treatment for posttraumatic stress disorder in war veterans. We will follow the scoping review process as previously described. The study question is as follows: "Which types of clinical research designs, study types, study durations, adverse events, and clinical outcomes have been reported regarding acupuncture therapy for posttraumatic stress disorder in military veterans?" We will perform a comprehensive search of Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus databases, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, and PsycArticles databases, as well as Chinese, Korean, and Japanese databases, from inception to June 2022. Data from the included studies will be collected and descriptively analyzed in relation to our research question. The extracted data will be collated, synthesized, and summarized according to the analytical framework of a scoping review. The protocol of this study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews to ensure the clarity and completeness of our reporting in all phases of this scoping review (Protocol registration: https://osf.io/t723f/). The findings of this scoping review will provide fundamental data that will help researchers identify appropriate research questions and design further studies on the use of acupuncture for PTSD management in military veterans. These results will be helpful for developing disaster site-specific research protocols for future clinical trials on this topic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exosomes, vehicles for intercellular communication, are formed intracellularly within multivesicular bodies (MVBs) and are released upon fusion with the plasma membrane. For their biogenesis, proper ...cargo loading to exosomes and vesicle traffic for extracellular release are required. Previously we showed that the L-type lectin, LMAN2, limits trans-Golgi Network (TGN)-to-endosomes traffic of GPRC5B, an exosome cargo protein, for exosome release. Here, we identified that the protein deacetylase sirtuin 2 (SIRT2) as a novel interactor of LMAN2. Loss of SIRT2 expression resulted in exosomal release of LMAN2, a Golgi resident protein, along with increased exosomal release of GPRC5B. Furthermore, knockout of SIRT2 increased total number of extracellular vesicles (EVs), indicating increased MVB-to-EV flux. While knockout of SIRT1 increased EV release with enlarged late endolysosome, knockout of SIRT2 did not exhibit endolysosome enlargement for increased EV release. Taken together, our study suggests that SIRT2 regulates cargo loading to MVBs and MVB-to-EV flux through a mechanism distinct from that of SIRT1.
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