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2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yan Ma ◽  
Xi Chen

Abstract Introduction Several antidiabetic medications have been proposed as prospective treatments for cognitive impairments in type 2 diabetes patients, glibenclamide (GBC) among them. Our research aimed to evaluate the impact of GBC on hippocampal learning memory and inflammation due to enhanced neurotrophic signals induced by inhalation of sevoflurane. Material and Methods Rats (Sprague Dawley, both sexes) were assigned to four groups: a control (vehicle, p.o.), GBC (10 mg/kg b.w.; p.o.), low-dose sevoflurane and low-dose sevoflurane + GBC (10 mg/kg b.w.; p.o.) for 23 days. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining was performed to analyse the count of apoptotic cells and ELISA was conducted to assess the protein signals. A Western blot, a Y-maze test, and a Morris maze test were performed, and the results analysed. Blood and tissues were collected, and isolation of RNA was performed with qRT-PCR. Results The Morris maze test results revealed an improvement in the length of the escape latency on days 1 (P < 0.05), 2 (P < 0.01), 3, and 4 in the low-dose Sevo group. Time spent in the quadrant and crossing axis and the percentage of spontaneous alterations showed a substantial decrease in the low-dose Sevo group which received GBC at 10 mg/kg b.w. Significant increases were shown in IL-6 and TNF-α levels in the low-dose Sevo group, whereas a decrease was evident in the GBC group. Conclusion Our results indicate that glibenclamide may be a novel drug to prevent sevoflurane inhalation-induced impaired learning and reduce brain-derived neurotrophic factor release, which may be a vital target for the development of potential therapies for cognitive deficits and neurodegeneration.


2021 ◽  
Author(s):  
Xiaowei He ◽  
Dan Wu ◽  
Yanan Xu ◽  
Yaqin Zhang ◽  
Yue Sun ◽  
...  

Abstract Perfluorooctanoic acid (PFOA), a widely used chemical substance, causes an increased risk of human type 2 diabetes (T2D) through a currently unknown mechanism. The aim of the present study was to investigate whether PFOA regulates the functions of pancreatic β cells, which are specialized for biosynthesis and secretion of insulin, and to reveal the underlying mechanism. Treatment of the MIN6 β-cell line with PFOA caused a time- and dose-dependent inhibition of cell viability in CCK-8 assays. Annexin V/PI and TUNEL staining results confirmed that exposure to a high PFOA dose (500 μM) promoted apoptosis of MIN6 cells, while a low dose (300 μM) had no effects on β-cell survival. PFOA treatment, even at a low dose, diminished glucose-stimulated insulin secretion (GSIS) in both primary islet perfusion and MIN6 cell experiments. Bulk RNA-sequencing data showed a significantly increased expression of endoplasmic reticulum (ER) stress-associated genes, with tribbles homolog 3 (Trib3) ranking first among the altered genes. Activation of ER stress pathways was verified by qRT-PCR assays, and the ATF4/CHOP/TRIB3 pathway contributed to PFOA-induced β-cell damage. Inhibition of TRIB3 expression significantly protected MIN6 cells from PFOA-induced GSIS defects and apoptosis by ameliorating ER stress. These findings reveal a link between ER stress and PFOA-induced β-cell defects, opening up an entirely new set of questions about the pathogenesis of T2D due to environmental chemicals.


Author(s):  
Joseph C. Watso ◽  
Mu Huang ◽  
Luke Belval ◽  
Frank A. Cimino III ◽  
Caitlin P. Jarrard ◽  
...  

Our knowledge about how low-dose (analgesic) fentanyl affects autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low-dose fentanyl influences human autonomic cardiovascular responses during painful stimuli in humans. Therefore, we tested the hypothesis that low-dose fentanyl reduces perceived pain and subsequent sympathetic and cardiovascular responses in humans during an experimental noxious stimulus. Twenty-three adults (10F/13M; 27±7 y; 26±3 kg•m-2, mean ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed a cold pressor test (CPT; hand in ~0.4 °C ice bath for two minutes) before and five minutes after drug/placebo administration (75 μg fentanyl or saline). We compared pain perception (100 mm visual analog scale), muscle sympathetic nerve activity (MSNA; microneurography, 11 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) between trials (at both pre- and post-drug/placebo time points) using paired, two-tailed t-tests. Before drug/placebo administration, perceived pain (p=0.8287), Δ MSNA burst frequency (p=0.7587), and Δ mean BP (p=0.8649) during the CPT were not different between trials. After the drug/placebo administration, fentanyl attenuated perceived pain (36 vs. 66 mm, p<0.0001), Δ MSNA burst frequency (9 vs. 17 bursts/minute, p=0.0054), and Δ mean BP (7 vs. 13 mmHg, p=0.0174) during the CPT compared to placebo. Fentanyl-induced reductions in pain perception and Δ mean BP were moderately related (r=0.40, p=0.0641). These data provide valuable information regarding how low-dose fentanyl reduces autonomic cardiovascular responses during an experimental painful stimulus.


2021 ◽  
Vol 8 ◽  
Author(s):  
Alaa El-Din H. Sayed ◽  
Kento Nagata ◽  
Takuya Nakazawa ◽  
Hiroshi Mitani ◽  
Junya Kobayashi ◽  
...  

Morphological alterations and nuclear abnormalities in fish erythrocytes have been used in many studies as bioindicators of environmental mutagens including ionizing radiation. In this study, adult Japanese medaka (Oryzias latipes) were irradiated with gamma rays at a low dose rate (9.92 μGy/min) for 7 days, giving a total dose of 100 mGy; and morphological alterations, nuclear abnormalities, and apoptotic cell death induced in peripheral erythrocytes were investigated 8 h and 7 days after the end of the irradiation. A variety of abnormalities, such as tear-drop cell, crenated cell, acanthocyte, sickled cell, micronucleated cell, eccentric nucleus, notched nucleus, and schistocyte, were induced in the peripheral erythrocytes of the wild-type fish, and a less number of abnormalities and apoptotic cell death were induced in the p53-deficient fish. These results indicate that low dose-rate chronic irradiation of gamma rays can induce cytotoxic and genotoxic effects in the peripheral erythrocytes of medaka, and p53-deficient medaka are tolerant to the gamma-ray irradiation than the wild type on the surface.


Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1320
Author(s):  
Antonio Pierro ◽  
Alessandro Posa ◽  
Costanzo Astore ◽  
Mariacarmela Sciandra ◽  
Alessandro Tanzilli ◽  
...  

Multiple myeloma is a hematological malignancy of plasma cells usually detected due to various bone abnormalities on imaging and rare extraosseous abnormalities. The traditional approach for disease detection was based on plain radiographs, showing typical lytic lesions. Still, this technique has many limitations in terms of diagnosis and assessment of response to treatment. The new approach to assess osteolytic lesions in patients newly diagnosed with multiple myeloma is based on total-body low-dose CT. The purpose of this paper is to suggest a guide for radiologists in performing and evaluating a total-body low-dose CT in patients with multiple myeloma, both newly-diagnosed and in follow-up (pre and post treatment).


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jianhua Hong

Objective. The study aimed to explore the application value of artificial intelligence (AI)-based low-dose digital subtraction angiography (DSA) in the care of maintenance hemodialysis (MHD) patients. Methods. The characteristics of DSA imaging were analyzed, and the refinement efficiency of the AI algorithm was discussed, expected to assist clinicians in the care and treatment of patients. 100 MHD patients who were in the hospital were selected as the research subjects. They were randomly divided into the conventional DSA group (conventional group) and the AI algorithm-based DSA group (AI-based DSA group). The conventional group used conventional DSA images to guide the care of HM patients, and the AI-based DSA group used the AI algorithm to optimize DSA images. Results. It was found that the AI-based DSA group was better than the conventional DSA group in terms of image sharpness and shaded areas, and the image mean square error (MSE) loss value was smaller ( P < 0.05 ). The patients were followed up for 3 months. In the AI-based DAS group, the blood flow of the drainage vein (DV), the blood flow of the proximal vein (PA), and the blood flow of the brachial artery (BA) were greater than those of the conventional group ( P < 0.05 ). During the 3-month follow-up period, in the conventional group, thrombosis occurred in 4 patients, low-flow AVF occurred in 5 patients, high-flow AVF occurred in 3 patients, and heart failure occurred in 5 patients. In the AI-based DSA group, thrombosis occurred in 2 patients, low-flow AVF occurred in 2 cases, high-flow AVF occurred in 1 case, and heart failure occurred in 3 cases. There were no other cardiac complications in both groups. Conclusion. DSA images optimized by the AI algorithm are suitable for clinical diagnosis and have practical application value.


Author(s):  
Maryam Vosoughian ◽  
Shideh Dabir ◽  
Mastaneh Dahi ◽  
Mohammadreza Moshari

In this report, we presented our experience in treating severe postpartum post-dural puncture headache with low-dose propofol. Short-term use of low-dose propofol provided rapid and complete relief of the headache without recurrence.


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