miR-590-3p protects against ischaemia/reperfusion injury in an oxygen-glucose deprivation and reoxygenation cellular model by regulating HMGB1/TLR4/MyD88/NF-κB signalling

miR-590-3p has been reported to be reduced in myocardial ischaemia-reperfusion (I/R) injury, but its specific role in cerebral I/R injury is still uncertain. Thus, we explored the function and mechanism of miR590-3p in cerebral I/R injury using a cellular model. miR-590-3p, high mobility group Box 1 (HMGB1), and signalling-related factor levels were assessed using qPCR or a western blot analysis. Cell apoptosis was measured by flow cytometry. Inflammatory factors were detected by ELISA. The target of miR-590-3p was confirmed by dual-luciferase reporter assay and western blot analysis. We found that miR-590-3p was decreased and HMGB1 was increased in the OGD/R model. Upregulation of miR-590-3p reduced cell apoptosis and inflammation in the OGD/R model, and the TLR4/MyD88/NF-κB signalling pathway was suppressed. However, inhibition of miR-590-3p showed the opposite effects. Moreover, HMGB1 was verified as a target gene of miR-590-3p. HMGB1 reversed the decrease in apoptosis and inflammation caused by overexpression of miR590-3p, and the TLR4/MyD88/NF-κB signalling pathway was activated. Our results suggest that miR-590-3p regulates the TLR4/MyD88/NF-κB pathway by interacting with HMGB1 to protect against OGD/R-induced I/R injury. Thus, miR-590-3p may serve as a potential therapeutic target in cerebral I/R repair

Severe Stroke Patients With Left-Sided Occlusion of the Proximal Anterior Circulation Benefit More From Thrombectomy

Background and Purpose: Endovascular thrombectomy improves the functional independence of patients with proximal anterior circulation occlusion. However, a subset of patients fail to benefit from thrombectomy procedures, the reasons for which remain poorly defined. In this study, we investigated whether the effectiveness of thrombectomy was affected by left- or right-sided occlusion among patients with similar stroke severities.Methods: Patients with proximal anterior circulation occlusion (internal carotid or M1 of middle cerebral artery) treated with the Solitaire stent retriever within 8 h of the onset of acute ischemic stroke were enrolled from the Yijishan Hospital of Wannan Medical College. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS) on admission. The functional outcomes were assessed using the modified Rankin scale (mRS) at 90 days.Results: We enrolled 174 patients including 90 left-sided occlusion and 84 right-sided occlusion. The NIHSS scores on admission were higher in the left-sided (median, 19; interquartile range, 16 to 20) compared to the right-sided occlusion group (median, 15, interquartile range, 13 to 18) (P < 0.001). Following adjustment for potential risk factors, patients with left-sided occlusion had higher rates of functional independence (mRS ≤ 2) and lower rates of mortality (mRS = 6) compared to the right-sided occlusion patients (39.5 vs. 19.6% and 28.9 vs. 47.8%, respectively) in the severe stroke group (NIHSS ≥ 15).Conclusions: In severe stroke patients with proximal anterior circulation occlusion, stent retriever thrombectomy within 8 h of the onset of symptoms provides more benefits to left-sided occlusion

Efficacy and safety of calcitonin gene‐related peptide antagonists in migraine treatment: A meta‐analysis

Abstract Introduction We systematically reviewed the efficacy and safety of Calcitonin Gene‐Related Peptide (CGRP) antagonists for migraine treatment. Methods Various databases including PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), WanFang Data were electronically searched for randomized controlled trials (RCTs) on CGRP antagonists for migraine treatment since inception to March 2021. The trials were screened for inclusion, after which the methodological quality of the included trials was assessed. Then meta‐analysis was performed using the Revman 5.3 software. Results A total of 26 RCTs involving 21,736 patients were included. The CGRP antagonists group included 13,635 patients while the control group included 8101 patients. Meta‐analysis showed that compared to the control group, CGRP antagonists were associated with various significant effects, including the following outcome indicators: (1) number of patients with ≥50% reduction from baseline in mean monthly migraine days (RR = 1.50, 95% CI [1.39,1.62], p < .00001); (2) number of patients with pain free at 2 h postdose (RR = 1.98, 95% CI [1.77, 2.20], p < .00001), and (3) number of patients with 2–24 h sustained pain free postdose (RR = 2.18, 95% CI [1.93, 2.46], p < .00001). However, the number of patients with any adverse events was significantly high in the antagonists group, relative to the control group (RR = 1.08, 95% CI [1.04, 1.12], p < .0001). Conclusions CGRP antagonists are significantly effective for migraine treatment; however, they are associated with various adverse events. Due to limitations with regards to quantity and quality of the included studies, the above conclusions should be verified by more high quality studies

The Pathogenesis of Necroptosis-Dependent Signaling Pathway in Cerebral Ischemic Disease

Necroptosis is the best-described form of regulated necrosis at present, which is widely recognized as a component of caspase-independent cell death mediated by the concerted action of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3). Mixed-lineage kinase domain-like (MLKL) was phosphorylated by RIPK3 at the threonine 357 and serine 358 residues and then formed tetramers and translocated onto the plasma membrane, which destabilizes plasma membrane integrity leading to cell swelling and membrane rupture. Necroptosis is downstream of the tumor necrosis factor (TNF) receptor family, and also interaction with NOD-like receptor pyrin 3 (NLRP3) induced inflammasome activation. Multiple inhibitors of RIPK1 and MLKL have been developed to block the cascade of signal pathways for procedural necrosis and represent potential leads for drug development. In this review, we highlight recent progress in the study of roles for necroptosis in cerebral ischemic disease and discuss how these modifications delicately control necroptosis

Directly wireless communication of human minds via non-invasive brain-computer-metasurface platform

Brain-computer interfaces (BCIs), invasive or non-invasive, have projected unparalleled vision and promise for assisting patients in need to better their interaction with the surroundings. Inspired by the BCI-based rehabilitation technologies for nerve-system impairments and amputation, we propose an electromagnetic brain-computer-metasurface (EBCM) paradigm, regulated by human’s cognition by brain signals directly and non-invasively. We experimentally show that our EBCM platform can translate human’s mind from evoked potentials of P300-based electroencephalography to digital coding information in the electromagnetic domain non-invasively, which can be further processed and transported by an information metasurface in automated and wireless fashions. Directly wireless communications of the human minds are performed between two EBCM operators with accurate text transmissions. Moreover, several other proof-of-concept mind-control schemes are presented using the same EBCM platform, exhibiting flexibly-customized capabilities of information processing and synthesis like visual-beam scanning, wave modulations, and pattern encoding

Graphene Sheet-Induced Global Maturation of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Human induced pluripotent stem cells (hiPSCs) can proliferate infinitely. Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling, drug screening and regenerative medicine. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) display a low degree of maturation and fetal-like properties. Current in vitro differentiation methods do not mimic the structural, mechanical, or physiological properties of the cardiogenesis niche. Recently, we present an efficient cardiac maturation platform that combines hiPSCs monolayer cardiac differentiation with graphene substrate, which is a biocompatible and superconductive material. The hiPSCs lines were successfully maintained on the graphene sheets and were able to differentiate into functional cardiomyocytes. This strategy markedly increased the myofibril ultrastructural organization, elevated the conduction velocity, and enhanced both the Ca²⁺ handling and electrophysiological properties in the absence of electrical stimulation. On the graphene substrate, the expression of connexin 43 increased along with the conduction velocity. Interestingly, the <i>bone morphogenetic proteins</i> signaling was also significantly activated during early cardiogenesis, confirmed by RNA sequencing analysis. Here, we reasoned that graphene substrate as a conductive biomimetic surface could facilitate the intrinsic electrical propagation, mimicking the microenvironment of the native heart, to further promote the global maturation of hiPSC-CMs. Our findings highlight the capability of electrically active substrates to influence cardiomyocyte development. We believe that application of graphene sheets will be useful for simple, fast, and scalable maturation of regenerated cardiomyocytes

The impact of interventions on appointment and clinical outcomes for individuals with diabetes: a systematic review

BACKGROUND: Successful diabetes disease management involves routine medical care with individualized patient goals, self-management education and on-going support to reduce complications. Without interventions that facilitate patient scheduling, improve attendance to provider appointments and provide patient information to provider and care team, preventive services cannot begin. This review examines interventions based upon three focus areas: 1) scheduling the patient with their provider; 2) getting the patient to their appointment, and; 3) having patient information integral to their diabetes care available to the provider. This study identifies interventions that improve appointment management and preparation as well as patient clinical and behavioral outcomes. METHODS: A systematic review of the literature was performed using MEDLINE, CINAHL and the Cochrane library. Only articles in English and peer-reviewed articles were chosen. A total of 77 articles were identified that matched the three focus areas of the literature review: 1) on the schedule, 2) to the visit, and 3) patient information. These focus areas were utilized to analyze the literature to determine intervention trends and identify those with improved diabetes clinical and behavioral outcomes. RESULTS: The articles included in this review were published between 1987 and 2013, with 46 of them published after 2006. Forty-two studies considered only Type 2 diabetes, 4 studies considered only Type 1 diabetes, 15 studies considered both Type 1 and Type 2 diabetes, and 16 studies did not mention the diabetes type. Thirty-five of the 77 studies in the review were randomized controlled studies. Interventions that facilitated scheduling patients involved phone reminders, letter reminders, scheduling when necessary while monitoring patients, and open access scheduling. Interventions used to improve attendance were letter reminders, phone reminders, short message service (SMS) reminders, and financial incentives. Interventions that enabled routine exchange of patient information included web-based programs, phone calls, SMS, mail reminders, decision support systems linked to evidence-based treatment guidelines, registries integrated with electronic medical records, and patient health records. CONCLUSIONS: The literature review showed that simple phone and letter reminders for scheduling or prompting of the date and time of an appointment to more complex web-based multidisciplinary programs with patient self-management can have a positive impact on clinical and behavioral outcomes for diabetes patients. Multifaceted interventions aimed at appointment management and preparation during various phases of the medical outpatient care process improves diabetes disease management