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Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk
No full text[[abstract]]Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found that CRISPR knockout of KDM5B in stem-cell-derived atrial cardiomyocytes led to a shortening of the action potential duration and widespread transcriptomic dysregulation of genes relevant to atrial homeostasis and conduction. Our results highlight the contribution of rare coding and structural variants to AF, including genetic links between AF and cardiomyopathies, and expand our understanding of the rare variant architecture for this common arrhythmia
The impact of sodium-glucose cotransporter-2 inhibitors on dialysis risk and mortality in kidney transplant patients with diabetes
No full text[[abstract]]Kidney transplantation is the optimal treatment for end-stage kidney disease, but many patients also have diabetes mellitus. This study compares long-term outcomes between new users of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in kidney transplant recipients with diabetes mellitus. Data from the TriNetX Collaborative Network, including 89,710 patients with diabetes mellitus who underwent kidney transplantation between January 1, 2015, and June 30, 2023, were analyzed. From this cohort, 1,410 matched pairs of SGLT2i and DPP-4i users were selected based on propensity scores. The results showed that SGLT2i users had a lower risk of dialysis (HR: 0.694) and all-cause mortality (HR: 0.687) compared to DPP-4i users. There were no significant differences in the risk of post-transplant infections, transplant rejection, or hospitalization between the two groups. Additionally, SGLT2i users had significantly lower cumulative incidences of dialysis and mortality. In conclusion, this study, utilizing data from TriNetX, demonstrates that SGLT2i treatment in kidney transplant recipients with diabetes mellitus is associated with lower risks of dialysis and mortality, suggesting it may help preserve kidney function and improve survival in this population
免疫抑制細胞作成方法,及び,免疫抑制細胞を含む組成物の使用方法
No full text[[abstract]]This invention relates to an immunosuppressive cell, and methods of obtaining the cell and using the cell. The immunosuppressive cell is obtained by culturing a precursor cell in a medium that contains a GRO chemokine
对抗肠病毒感染的基于腺病毒载体的疫苗
No full text[[abstract]]本发明关于一种重组腺病毒载体，可用于产生免疫力以对抗肠病毒感染。于一具体实施例中，本发明之重组腺病毒载体包含一表现卡匣，其编码肠病毒之P1蛋白及3CD蛋白酶。于另一具体实施例中，本发明重组腺病毒载体包含一表现卡匣，其编码肠病毒之3C蛋白酶或3CD蛋白酶。本发明亦关于一种疫苗组合物，包含所述之重组腺病毒载体。本发明提供一种使用该重组腺病毒载体及疫苗组合物以诱发个体产生免疫反应，对抗肠病毒感染的方法。进一步提供一种产生肠病毒之类病毒颗粒之方法，系藉由表现本文所述之腺病毒载体于哺乳动物细胞中
Method and composition for treatment of hair loss
No full text[[abstract]]A method of treating a hair loss condition, comprising administering a Notch signaling pathway activator to a subject in need thereof
Method of producing exosomes from stem cells and use thereof
No full text[[abstract]]A method of producing induced exosomes, the method comprising: contacting an isolated population of stem cells with an amount of a prostaglandin E receptor 4 (EP4) antagonist effective for inducing release of exosomes, whereby induced exosomes are released from the stem cells, and isolating the induced exosomes
Methods to enhance nerve regeneration utilizing neural stem cells and IL12P40
No full text[[abstract]]The present application provides a composition and methods to enhance nerve regeneration utilizing at least one component of neural stem cells or IL12p40. The composition comprises neural stem cells and a neurotrophic factor, which is constructed by IL12p40 as at least one subunit. The methods to enhance nerve regeneration comprise providing a nerve regeneration composition comprising a neurotrophic factor containing IL12p40 as at least one subunit to a subject. The composition of the methods can further comprise neural stem cells
The potential usage of mmp-9 upregulation in predicting hemorrhagic transformation after endovascular thrombectomy
No full text[[abstract]]Background and Aims: Hemorrhagic transformation (HT) is a serious complication after endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS). We analyzed the plasma levels of MMP-9 before and after EVT, and assessed the temporal changes of MMP-9 in predicting HT after EVT. Methods: We enrolled 30 AIS patients who received EVT, and 16 of them (53.3%) developed HT. The levels of plasma MMP-9 collected from the arteries of AIS patients before and immediately after EVT were meas-ured using ELISA. The percentage changes of MMP-9 after EVT (after/before) were calculated and compared between patients with and with-out HT. Results: The median age of AIS patients was 70, and 13 of them (43.3%) were men. The median National Institutes of Health Stroke Scale (NIHSS) of patients with HT was 18 on admission and 18 after EVT. The NIHSS of patients without HT was 17 on admission and 11 after EVT. Patients with HT demonstrated significantly greater percentage increases in arterial MMP-9 levels after EVT. Conclusions: In AIS patients who developed HT, there was a signifi-cant increase in arterial MMP-9 levels after EVT, suggesting that the upregulation of MMP-9 following EVT could serve as a predictive bio-marker for HT
Epithelial cell adhesion molecule induces induces Wnt receptor transcription to promote colorectal cancer progression
No full text[[abstract]]Epithelial cell adhesion molecule (EpCAM) has been widely studied as a tumour antigen due to its expression in varieties of solid tumours. Moreover, the glycoprotein contributes to critical cancer-associated cellular functionalities via its extraceullar (EpEX) and intraceullar (EpICD) domains. In colorectal cancerb (CRC), EpCAM has been implicated in the Wnt signaling pathway, as EpICD and B-Catenin are coordinately translocated to the nucleus. Once in the nucleus, EpICD transcriptionally regulates EpCAM target genes. Here, we studied the role of EpCAM in colorectal cancer (CRC) stemness. We found that the EpEX-induced Wnt signaling activated TACE and γ-secretase enzymes to augment shedding of EpEX and EpICD, establishing a positive feedback loop. Importantly, we show that the EpICD interacted with the promoters of Wnt receptors (FZD6 and LRP5/6) thus upregulated their transcriptional activity inducing Wnt signaling. Furthermore, activation of Wnt-pathway-associated kinases in the β-Catenin destruction complex (GSK3β and CK1) induced γ-secretase activity to augment EpICD shedding, establishing a positive-feedback loop. Our EpCAM-neutralizing antibody (EA2-6) and a porcupine inhibitor (LGK974) each partially attenuated acncer stemness, while their combination abolished stemness-related endpoints, induced apoptosis in vitro and markedly diminished tumour progression in animal moedls of human CRC. From these findings, we conclued that EpCAM stimulates Wnt signaling to promote cancer stemness, and the combination of EpAb2-6 and porcupine inhibitors may represent an effective CRC treatment, including for KRAS-mutant cancers. Thus. the mechanistic insights gained from our study may be useful to improve existin treatments or to develop novel anticancer therapeutics
Gamma knife radiosurgery for orbital cavernous hemangioma: A systematic review and single-arm meta-analysis
No full text[[abstract]]Gamma knife radiosurgery (GKRS) for orbital cavernous hemangioma (OCH) has emerged as a promising method due to its significant clinical improvement and low incidence of complications. This study aimed to evaluate the safety and efficacy of GKRS for the treatment of OCH. Following the PRISMA framework, we searched PubMed, Cochrane Central, and Embase for studies reporting outcomes of GKRS for OCH, including complications, visual improvement, proptosis, tumor reduction rate, and tumor progression rate. From 1856 search results, six studies with 100 patients were included. Only five minor complications related to GKRS were reported, including three with orbital pain and two with periorbital chemosis, resulting in a complication rate of 13% (95% CI: 7% - 25%). Visual acuity and visual field improvement rates after GKRS were 80% (95% CI: 63% - 96%) and 71% (95% CI: 47% - 95%), respectively. Proptosis improved in 94% of cases (95% CI: 83% - 100%). The tumor reduction rate was 77% after GKRS (95% CI: 69% - 85%). In conclusion, GKRS for OCH appears to be a safe technique, as evidenced by the rate of clinical improvement and radiological improvement. However, studies are limited by the absence of a control group, and additional studies are needed to evaluate the relative efficacy of GKRS compared with alternative surgical modalities for OCH