Serum miR-195-5p Exhibits Clinical Significance in the Diagnosis of Essential Hypertension with Type 2 Diabetes Mellitus by Targeting DRD1

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM

Using MemTrax memory test to screen for post-stroke cognitive impairment after ischemic stroke: a cross-sectional study

BackgroundWhereas the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s cognitive examination-revised (ACE-R) are commonly used tests for the detection of post-stroke cognitive impairment (PSCI), these instruments take 10–30 min to administer and do not assess processing speed, which is a critical impairment in PSCI. MemTrax (MTx) is a continuous recognition test, which evaluates complex information processing, accuracy, speed, and attention, in 2 min.AimTo evaluate whether MTx is an effective and practical tool for PSCI assessment.MethodsThis study enrolled acute ischemic stroke (AIS) patients who have assessed the cognitive status including MTx, clinical dementia rating (CDR), MoCA, Neuropsychiatric Inventory (NPI), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), the National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), and Barthel Index of activity of daily living (BI) combined with the physical examinations of the neurologic system at the 90-day (D90) after the AIS. The primary endpoint of this study was establishing MTx cut-offs for distinguishing PSCI from AIS.ResultsOf the 104 participants, 60 were classified to the PSCI group. The optimized cut-off value of MTx-%C (percent correct) was 78%, with a sensitivity and specificity for detecting PSCI from Non-PSCI of 90.0 and 84.1%, respectively, and an AUC of 0.919. Regarding the MTx-Cp (Composite score = MTx-%C/MTx-RT), using 46.3 as a cut-off value, the sensitivity and specificity for detecting PSCI from Non-PSCI were 80.0 and 93.2%, with an AUC of 0.925. Multivariate linear regression showed that PSCI reduced the MTx-%C (Coef. −14.18, 95% CI −18.41∼−9.95, p < 0.001) and prolonged the MTx-RT (response time) (Coef. 0.29, 95% CI 0.16∼0.43, p < 0.001) and reduced the MTx-CP (Coef. −19.11, 95% CI −24.29∼−13.93, p < 0.001).ConclusionMemTrax (MTx) is valid and effective for screening for PSCI among target patients and is a potentially valuable and practical tool in the clinical follow-up, monitoring, and case management of PSCI

Arsenic and antimony co-induced nephrotoxicity via autophagy and pyroptosis through ROS-mediated pathway in vivo and in vitro

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl3) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 μM), SbCl3 (25 μM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity

Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study

Background The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. Methods Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. Results Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. Conclusions Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. Trial registration ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019

Image_1_Using MemTrax memory test to screen for post-stroke cognitive impairment after ischemic stroke: a cross-sectional study.pdf

BackgroundWhereas the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s cognitive examination-revised (ACE-R) are commonly used tests for the detection of post-stroke cognitive impairment (PSCI), these instruments take 10–30 min to administer and do not assess processing speed, which is a critical impairment in PSCI. MemTrax (MTx) is a continuous recognition test, which evaluates complex information processing, accuracy, speed, and attention, in 2 min.AimTo evaluate whether MTx is an effective and practical tool for PSCI assessment.MethodsThis study enrolled acute ischemic stroke (AIS) patients who have assessed the cognitive status including MTx, clinical dementia rating (CDR), MoCA, Neuropsychiatric Inventory (NPI), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), the National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), and Barthel Index of activity of daily living (BI) combined with the physical examinations of the neurologic system at the 90-day (D90) after the AIS. The primary endpoint of this study was establishing MTx cut-offs for distinguishing PSCI from AIS.ResultsOf the 104 participants, 60 were classified to the PSCI group. The optimized cut-off value of MTx-%C (percent correct) was 78%, with a sensitivity and specificity for detecting PSCI from Non-PSCI of 90.0 and 84.1%, respectively, and an AUC of 0.919. Regarding the MTx-Cp (Composite score = MTx-%C/MTx-RT), using 46.3 as a cut-off value, the sensitivity and specificity for detecting PSCI from Non-PSCI were 80.0 and 93.2%, with an AUC of 0.925. Multivariate linear regression showed that PSCI reduced the MTx-%C (Coef. −14.18, 95% CI −18.41∼−9.95, p ConclusionMemTrax (MTx) is valid and effective for screening for PSCI among target patients and is a potentially valuable and practical tool in the clinical follow-up, monitoring, and case management of PSCI.</p