Gaucher disease (GD) is one of the most common lysosomal storage disorders and is caused by an inherited deficiency in glucocerebrosidase. Dipeptidyl peptidase-4 inhibitors have demonstrated multiple beneficial activities, including anti-diabetic, anti-oxidant, anti-apoptotic, and neuroprotective effects. The aim of this study was to determine if omarigliptin, a dipeptidyl peptidase-4 inhibitor, has a therapeutic effect on fibroblast cells derived from patients with type II GD. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of omarigliptin on cell viability. The expression patterns of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3-binding protein (E3BP), and citrate synthase (CS) were evaluated by western blotting to characterize the effect of omarigliptin treatment on GD cells. Thin-layer chromatography (TLC) was performed to determine glucosylceramide levels in omarigliptin-treated GD cells. Omarigliptin increased GD cell viability compared to untreated control cells. Further, omarigliptin treatment dose-dependently decreased the apoptotic factors AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of intracellular glucosylceramides in omarigliptin-treated GD cells. These findings demonstrate that omarigliptin can reduce cellular stress resulting from glucosylceramide accumulation, and suggest that omarigliptin should be studied further as a novel therapeutic agent for GD.
Gaucher disease is the most common lysosomal storage disorder. Resveratrol is a phytoalexin that possesses a wide range of beneficial effects, including anti-inflammatory, anti-oxidant, and neuroprotective properties. This study was conducted to determine whether the resveratrol derivative HG-101 has a therapeutic effect on primary fibroblast cells derived from patients with type III Gaucher disease. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of HG-101 on cell survival. The expression levels of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3-binding protein (E3BP), and citrate synthase (CS) were evaluated by western blotting to characterize the effect of HG-101 treatment on Gaucher disease cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in HG-101-treated patient cells. HG-101 increased the viability of patient cells compared to that of untreated control cells. HG-101 treatment dose-dependently decreased AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of glucosylceramides in HG-101-treated patient cells. These findings demonstrate that the resveratrol derivative HG-101 can relieve cellular stress due to glucosylceramide accumulation, and suggest that it should be studied further as a new therapeutic approach for the treatment of neuronopathic Gaucher disease.
Gaucher disease (GD) is the most prevalent lysosomal storage disorder caused by an inherited deficiency of glucocerebrosidase. In the present study, we aimed to determine whether dipeptidyl peptidase-4 inhibitors (DPP4i) exhibit a potential therapeutic effect in type I GD cells. Four kinds of DPP4i were tested in dermal fibroblasts from patients with type I GD. MTT assays were performed to determine their effects on cell viability. The expression levels of Bcl-2-associated X protein (Bax), ATP-citrate synthase (ATP-CS), E3-binding protein (E3BP), and acetyl-coenzyme A acetyltransferase 1 (ACAT1) were determined by western blotting to understand the molecular mechanism of DPP4i in cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in cultured fibroblasts. This investigation showed that DPP4i increased cell viability more than 1.45 times. After exposure to DPP4i, the expression level of Bax decreased, whereas those of ATP-CS, E3BP, and ACAT1 increased. TLC revealed reduced amounts of intracellular glucosylceramides in type I GD patient cells. Here, we suggest that DPP4i can reduce cellular stress by glucosylceramide accumulation, and that it may be utilized as a new therapeutic approach for Gaucher disease.
We consider estimation problems for linear systems with random matrices and additive uncertain disturbances. Information sets containing true states of the systems are defined and investigated. The sets are described by its support functions. Some theorems\non the approximation of the sets by be simpler objects are given. Particular cases, where matrices of the systems or probability spaces have special formes, are elaborated. In conclusion we review some examples.
The Internet has made information exchange easier and efficient, but it has also created a new space where criminals and terrorists can operate almost undetected. This paper tries to pinpoint the particular set of users who are operating covertly and sustain the level of trust on non-traditional social media subject to socio-technical attack. It may bring the negative psychological change in a person which may affect the decision making capability of a person, effect sentiments, invoke radicalization, and polarize the people towards some issue. This can create unrest in society in the form of outrage, civil war, genocides, etc. This paper proposes a model to find latent correlation among nodes of the social network filtering out a pool of hidden users operating covertly within the network. The proposed methodology also handles the problem of data sparsity and complexity associated with social network data.
The aim of the work – to elaborate the methods of aerobic endurance development in blind schoolchildren by means of natural running. Material and methods. 39 blind children of the boarding school were studied: 16 pupils of the 2-4 grades, 12 pupils of the 6-8 grades and 11 pupils of the 10-12 grades. Control groups included 40 schoolchildren of the ordinary schools with normal vision – 16 pupils of the 2-4 grades and two groups of 12 pupils of the 5-8 and 10-11 grades. 1 stage of studies – investigation of the possibility of schoolchildren sensory systems to provide orientation for blind and sighted children in the gym. 2 stage of studies – examination of the possibility of blind children to use different running options. 3 stage of studies – research of the ability of blind schoolchildren to perform running exercises in different modes, with different durations and intensities in order to develop a program to increase aerobic endurance by means of conditioning training and the device developed by us. Results. A survey of blind schoolchildren indicated a negative attitude towards running on the spot and unwillingness to use it both by middle and high school children (16.6%). Running with a guide was rejected by 50% of the blind aged 11-15 and 36.4% of older children. 54.5% of senior schoolchildren liked exercising on the simulators, whereas junior schoolchildren did not like it at all – 16.6% of positive answers. Most schoolchildren also did not approve the comfortability of known methods for developing aerobic endurance (Table 2). At the same time, comfortability and desire to use the developed device were approved by the majority of blind middle schoolchildren (91.7%) and 100% of senior schoolchildren. The developed program for conditioning training was aimed at the development of aerobic endurance in running with the use of suggested device, and allowed schoolchildren to significantly increase the number of meters covered in a standard set time. Conclusions. The most preferred sensory system for use in correcting the direction of blind pupil movement during running exercises is their tactile sensory system. The designed technical device is an efficient means for correcting and maintaining the direction of blind children movement during running in the gym using tactile sensations. Suggested method for aerobic endurance increase is an effective tool that can be used in conditioning training of blind pupils of middle and senior school age.
In Wuhan city of China, an episode of novel coronavirus (COVID-19) happened. during late December and it has quickly spread to all places in the world. Until May 29, 2020, cases were high in the USA with 1.7 Million, Russia with approximately 387 thousand, the UK with 271 thousand confirmed cases. Everybody on the planet is anxious to know when the coronavirus pandemic will end. In this scourge, most nations force extreme medication measures to contain\nthe spread of COVID-19. Modeling has been utilized broadly by every national government and the World Health Organization in choosing the best procedures to seek after in relieving the impacts of COVID-19. Many epidemiological models are studied to understand the spread of the\nillness and its prediction to find maximum capacity for human-to-human transmission so that control techniques can be adopted. Also, arrangements for the medical facilities required such as hospital beds and medical supplies can be made in advance. Many models are used to anticipate the results keeping in view the present scenario. There is an urgent need to study the various models and their impacts. In this study, we present a systematic literature review on epidemiological models for the outbreak of novel coronavirus in India. The epidemiological models with environmental parameters such as water, temperature, humidity, and air on the dynamics of COVID-19 is also studied. Here, In addition, an attempt to take out the results from the exploration and comparing it with the real data. The study helps to choose the models that\nare progressive and dependable to predict and give legitimate methods for various strategies.