scholarly journals Betaine Induced Autophagy to Protect Neurons Against Amyloid Beta in Alzheimer’s Disease

2021 ◽  
Author(s):  
Qingmian Meng ◽  
Yan Chen ◽  
Ying Chen ◽  
Lijun Wang ◽  
Lan Zhao
Keyword(s):  
Confocal Microscopy ◽  
Alzheimer Disease ◽  
Western Blot ◽  
Protective Effect ◽  
Amyloid Beta ◽  
Akt Pathway ◽  
Beta Actin ◽  
Autophagy Induction ◽  
Student’S T ◽  
Student’S T Test

Abstract Background: Alzheimer disease is a neurodegenerative disease, which is accompanied by the accumulation of amyloid beta and tau hyper phosphorylation. The objective of this study is to investigate amyloid-beta clearance through autophagy in HMC3 cells by betaine.Methods: In this study HMC3 cells were used. LC3, P62, p-AKT, p-MTOR, Beclin1, ATG 5, ATG 7, ATG 12 and beta-actin were studied by western blot. LC3 was studied by confocal microscopy. Neuroprotection and cell viability were assessed by MTT assay. Confocal microscopy and ELISA studied amyloid-beta clearance. Student's T-test was used to compare the treated vs untreated groups.Results: We have identified betaine an autophagy inducer in microglia HMC3 cells. We have further tried to establish the mechanism of betaine for autophagy induction. Betaine was able to induce autophagy through the PI3K/AKT pathway. Further, we investigated the clearance of amyloid-beta by betaine through autophagy induction. Betaine was also able to reduce the toxicity of amyloid-beta in human SHSY-5Y cells. A known down of LC3 reverses the protective effect of betaine against amyloid-beta in differentiated SHSY5Y cells.Conclusion: Betaine induced autophagy, clears amyloid-beta and protects SHSY-5Y cells against amyloid-beta. Based on these data, betaine can be further studied for anti-Alzheimer therapy.

G-lymphatic, vascular and immune pathways for Aβ clearance cascade and therapeutic targets for Alzheimer’s disease

2020 ◽  
Vol 23 ◽  
Author(s):  
Saurav Chakraborty ◽  
Jyothsna ThimmaReddygari ◽  
Divakar Selvaraj
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Complement System ◽  
Therapeutic Targets ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Amyloid Beta Peptide ◽  
Beta Peptide ◽  
Immune Pathways

The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of accumulation of extracellular amyloid beta peptides. Here, the clearance of amyloid beta peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines and the complement system also have a major role in Alzheimer disease. The physiological clearance pathways involved in amyloid beta peptide are glymphatic, vascular and immune pathways. Amyloid precursor protein, low density lipoprotein receptor-related protein 1, receptor for advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines and microglia are involved in amyloid beta peptide clearance pathways across the blood brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid beta agglomeration. This insoluble amyloid beta leads to neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

Microneedle-Assisted Percutaneous Transport of Magnesium Sulfate

2020 ◽  
Vol 17 (2) ◽  
pp. 140-147
Author(s):  
Karna B. Ghimirey ◽  
Kevin Ita
Keyword(s):  
Confocal Microscopy ◽  
Stratum Corneum ◽  
Magnesium Sulfate ◽  
Inductively Coupled Plasma ◽  
Optical Emission ◽  
Magnesium Concentration ◽  
Porcine Skin ◽  
Time Curve ◽  
Student’S T

Objective: In vitro diffusion experiments were performed to assess the permeation of magnesium sulfate across pig skin. Method: The mean thickness of the dermatomed porcine skin was 648 ± 12 µm. Magnesium concentration was measured using inductively coupled plasma-optical emission spectroscopy. Transdermal flux of magnesium sulfate across MN-treated and untreated porcine skin was obtained from the slope of the steady-state linear portion of cumulative amount versus time curve. Results: Statistical analysis of the results was done with Student’s t-test. The transdermal flux of magnesium sulfate across microneedle-treated porcine skin was 134.19 ± 2.4 µg/cm2/h and transdermal flux across untreated porcine skin was 4.64 ± 0.05 µg/cm2/h. Confocal microscopy was used to visualize the microchannels created by a solid microneedle roller (500 µm). Conclusion: From our confocal microscopy studies, it was evident that the 500 μm long microneedles disrupted the stratum corneum and created microchannels measuring 191 ± 37 µm. The increase in transdermal flux across the microneedle-treated skin was statistically significant compared to that of controls, i.e., without the application of microneedles. With the application of microneedles, the transdermal flux of magnesium permeated over 12 h was approximately 33-fold higher in comparison to passive diffusion across an intact stratum corneum.

Serosal and cutaneous recordings of gastric myoelectrical activity in patients with gastroparesis

1994 ◽  
Vol 266 (1) ◽  
pp. G90-G98 ◽  
Author(s):  
J. D. Chen ◽  
B. D. Schirmer ◽  
R. W. McCallum
Keyword(s):  
Electrical Stimulation ◽  
Slow Wave ◽  
Test Meal ◽  
Frequency Change ◽  
Fasting State ◽  
Gastric Myoelectrical Activity ◽  
Myoelectrical Activity ◽  
Gastric Slow Wave ◽  
Student’S T ◽  
Student’S T Test

The aims of this study were to 1) investigate gastric myoelectrical activity in patients with gastroparesis, 2) validate the cutaneous electrogastrogram (EGG) in tracking the frequency change of the gastric slow wave, and 3) investigate the effect of electrical stimulation on gastric myoelectrical activity. Gastric myoelectrical activity was recorded in 12 patients with documented gastroparesis using serosal electrodes for > 200 min in each subject. All recordings were made at least 4 days after surgery. Each session consisted of a 30-min recording in the fasting state and a 30-min recording after a test meal. The test meal (liquid or mixed) was selected according to patient's tolerance. Electrical stimulation was performed in three subjects via the serosal electrodes at a frequency of 3 cycles/min. Gastric myoelectrical activity was recorded using serosal electrodes in each session. The serosal recording showed slow waves of 2.5 to 4.0 cycles/min in all 12 subjects. Absence of spikes was noted in 11 of the 12 subjects. The simultaneous serosal and cutaneous recording of gastric myoelectrical activity showed that the frequency of the EGG was exactly the same as that of the serosal recording. Liquid meals resulted in a significant decrease in slow-wave frequency (Student's t test, P = 0.006), and the EGG accurately reflected this change. Electrical stimulation had no effect on the frequency of the gastric slow wave and did not induce spikes.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Changes in Dialysate Volume on Glucose and Urea Equilibration

1994 ◽  
Vol 14 (3) ◽  
pp. 236-239 ◽  
Author(s):  
Edward C. Kohaut ◽  
F. Bryson Waldo ◽  
Mark R. Benfield
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Prospective Study ◽  
Body Surface ◽  
Patient Population ◽  
Different Ages ◽  
Student’S T ◽  
A Prospective Study ◽  
Dialysate Volume ◽  
Student’S T Test

Objectives To determine the effect of changing dialysate volume on urea and glucoseequilibration curves and to determine, if dialysate volume is prescribed on the basis of body surface area, whether equilibration curves will be consistent in patients of different sizes and ages. Design A prospective study wherein children with acute or chronic renal failure had peritoneal equilibration studies done with dwell volumes of 30 mL/kg, 40 mL/kg, and 1200 mL/m2. Patient Population Twenty-two children: 7 under 3 years of age; 8 between 3 and 10 years of age; 7 older than 10 years of age. Statistics Student's t-test. Results Urea and glucose equilibrated rapidly at dwell volumes of 30 mL/kg, slower at dwell volumes of 40 mL/kg, and slowest at dwell volumes of 1200 mL/m2. Equilibration curves were similar in children of different ages when dialysate volumes of 1200 mL/m2 were infused. Conclusion Dialysate volumes of 1200 mL/m2 should be used when equilibration studies are being done to compare individuals of different ages and sizes.

scholarly journals SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhiya Deng ◽  
Maomao Sun ◽  
Jie Wu ◽  
Haihong Fang ◽  
Shumin Cai ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Cell Model ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Autophagy Induction ◽  
Promising Therapeutic Approach ◽  
Related Proteins ◽  
Caecal Ligation And Puncture

AbstractOur previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

scholarly journals Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1656
Author(s):  
Nataliya E. Kuz’mina ◽  
Sergey V. Moiseev ◽  
Mikhail D. Khorolskiy ◽  
Anna I. Lutceva
Keyword(s):  
Test Procedure ◽  
Active Pharmaceutical Ingredient ◽  
Test Methods ◽  
Intermediate Precision ◽  
Coefficients Of Variation ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Student’S T ◽  
Development And Validation ◽  
Student’S T Test

The authors developed a 1H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher’s F test, and Student’s t-test for assay results. The obtained statistical values satisfy the acceptance criteria for the validation parameters. The authors compared the results of impurity A quantification in gabapentin APIs and capsules by using the 1H qNMR and HPLC test methods.

scholarly journals Potential intravenous drug incompatibilities in a pediatric unit

2016 ◽  
Vol 14 (2) ◽  
pp. 185-189 ◽  
Author(s):  
Karla Dalliane Batista Leal ◽  
Ramon Weyler Duarte Leopoldino ◽  
Rand Randall Martins ◽  
Lourena Mafra Veríssimo
Keyword(s):  
Risk Factors ◽  
University Hospital ◽  
Intravenous Drug ◽  
Penicillin G ◽  
Cross Sectional ◽  
Relative Risks ◽  
Related Risk ◽  
Student’S T ◽  
Level Of Significance ◽  
Student’S T Test

ABSTRACT Objective To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. Methods A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student’s t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval. Results A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility. Conclusion Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities.

Dietary selenomethionine ameliorates lipopolysaccharide-induced renal inflammatory injury in broilers via regulating the PI3K/AKT pathway to inhibit necroptosis

2021 ◽  
Author(s):  
Yue Zhang ◽  
Xue Qi ◽  
Xiaoming Chen ◽  
Jinxi Zhang ◽  
Wenyue Zhang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Molecular Mechanism ◽  
Mechanism Of Action ◽  
Kidney Tissue ◽  
Akt Pathway ◽  
Inflammatory Injury ◽  
Molecular Mechanism Of Action

We explore the protective effect of dietary SeMet on the kidney tissue of broilers and determine its potential molecular mechanism of action.

scholarly journals Indicators of Targeted Physical Fitness in Judo and Jujutsu—Preliminary Results of Research

2021 ◽  
Vol 18 (8) ◽  
pp. 4347
Author(s):  
Wojciech J. Cynarski ◽  
Jan Słopecki ◽  
Bartosz Dziadek ◽  
Peter Böschen ◽  
Paweł Piepiora
Keyword(s):  
Reaction Time ◽  
Visual Stimulation ◽  
Intrinsic Value ◽  
Reaction Times ◽  
Arithmetic Means ◽  
Simple Reaction ◽  
Martial Art ◽  
Student’S T ◽  
Pearson Correlations ◽  
Student’S T Test

(1) Study aim: This is a comparative study for judo and jujutsu practitioners. It has an intrinsic value. The aim of this study was to showcase a comparison of practitioners of judo and a similar martial art jujutsu with regard to manual abilities. The study applied the measurement of simple reaction time in response to a visual stimulus and handgrip measurement. (2) Materials and Methods: The group comprising N = 69 black belts from Poland and Germany (including 30 from judo and 39 from jujutsu) applied two trials: “grasping of Ditrich rod” and dynamometric handgrip measurement. The analysis of the results involved the calculations of arithmetic means, standard deviations, and Pearson correlations. Analysis of the differences (Mann–Whitney U test) and Student’s t-test were also applied to establish statistical differences. (3) Results: In the test involving handgrip measurement, the subjects from Poland (both those practicing judo and jujutsu) gained better results compared to their German counterparts. In the test involving grasping of Ditrich rod, a positive correlation was demonstrated in the group of German judokas between the age and reaction time of the subjects (rxy = 0.66, p < 0.05), as well as in the group of jujutsu subjects between body weight and the reaction time (rxy = 0.49, p < 0.05). A significant and strong correlation between handgrip and weight was also established for the group of German judokas (rxy = 0.75, p < 0.05). In Polish competitors, the correlations were only established between the age and handgrip measurements (rxy = 0.49, p < 0.05). (4) Conclusions: Simple reaction times in response to visual stimulation were shorter in the subjects practicing the martial art jujutsu. However, the statement regarding the advantage of the judokas in terms of handgrip force was not confirmed by the results.

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