Pub Date : 2019-07-09DOI: 10.3390/MOL2NET-05-06239
Aline Ruiz Ceja, Astrid Varela Arzate, L. Cornejo
A considerable amount of human infections take place in mucous of the body, which is the reason why it is important to trigger immunological protection in this area. Even though parenteral administration of antigen induces efficient systemic protection, mucous from the body keep unprotected. Although attempts have been made to activate immunological protection in mucous membranes through different routes of application, some of them have had side effects or the desired effect has not been achieved clinically. Nasal mucosa route has been studied for drug administration and for vaccines application in recent years using peptides/proteins or genetic structure materials. Among the advantages reported on this material, due to the nature of these ingredients, it is susceptible to enzymatic degradation processes, so its half-life is very short. In addition, they are not able to easily cross the mucous membranes of the body or the biological membranes. This led to the research and development of nanocarriers as coadyuvants, to protect these materials and give them more stability.Research shows that mucosal vaccination has advantages over intramuscular immunization when it comes to provides mucosal protection, probably the most important of them is the fact that intranasal administration induces humoral and cellular immunity, which allows immunization at different mucosal sites as well as nasal mucosa, as well as systemic protection.
{"title":"NANOEMULSIONS AS COADYUVANTS IN INTRANASAL VACCINES","authors":"Aline Ruiz Ceja, Astrid Varela Arzate, L. Cornejo","doi":"10.3390/MOL2NET-05-06239","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06239","url":null,"abstract":"A considerable amount of human infections take place in mucous of the body, which is the reason why it is important to trigger immunological protection in this area. Even though parenteral administration of antigen induces efficient systemic protection, mucous from the body keep unprotected. Although attempts have been made to activate immunological protection in mucous membranes through different routes of application, some of them have had side effects or the desired effect has not been achieved clinically. Nasal mucosa route has been studied for drug administration and for vaccines application in recent years using peptides/proteins or genetic structure materials. Among the advantages reported on this material, due to the nature of these ingredients, it is susceptible to enzymatic degradation processes, so its half-life is very short. In addition, they are not able to easily cross the mucous membranes of the body or the biological membranes. This led to the research and development of nanocarriers as coadyuvants, to protect these materials and give them more stability.Research shows that mucosal vaccination has advantages over intramuscular immunization when it comes to provides mucosal protection, probably the most important of them is the fact that intranasal administration induces humoral and cellular immunity, which allows immunization at different mucosal sites as well as nasal mucosa, as well as systemic protection.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117241457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-09DOI: 10.3390/MOL2NET-05-06240
Astrid Varela Arzate, Aline Ruiz Ceja, L. Cornejo
Hydrogels are polymeric networks with a three-dimensional structure that promise a therapeutic revolution in tissue engineering, especially in the cardiovascular field. All due to its properties, probably the most important of them, its capacity to retain a big level of water and another substance. These smart biomaterials can be made of: proteins, peptides, polysaccharides or synthetic polymer. The present paper focusses on the most promising advances with hydrogels in the cardiovascular field in the last 5 years: The birth to a new generation of implants, Innovation of myocardial patches, Disclosure of injectable delivery system for vasculogenesis and cardiac repair, Modernization of cardiac repair using peptide hydrogels from human umbilical cord mesenchymal stem cell derived exosomes, Novel result with the injection of a recombinant human collagen hydrogel to improve cardiac function and reduce pathological remodeling after an acute myocardial infarction.
{"title":"CARDIOVASCULAR THERAPEUTIC PROPERTIES OF NANOSTRUCTURED HYDROGELS","authors":"Astrid Varela Arzate, Aline Ruiz Ceja, L. Cornejo","doi":"10.3390/MOL2NET-05-06240","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06240","url":null,"abstract":"Hydrogels are polymeric networks with a three-dimensional structure that promise a therapeutic revolution in tissue engineering, especially in the cardiovascular field. All due to its properties, probably the most important of them, its capacity to retain a big level of water and another substance. These smart biomaterials can be made of: proteins, peptides, polysaccharides or synthetic polymer. The present paper focusses on the most promising advances with hydrogels in the cardiovascular field in the last 5 years: The birth to a new generation of implants, Innovation of myocardial patches, Disclosure of injectable delivery system for vasculogenesis and cardiac repair, Modernization of cardiac repair using peptide hydrogels from human umbilical cord mesenchymal stem cell derived exosomes, Novel result with the injection of a recombinant human collagen hydrogel to improve cardiac function and reduce pathological remodeling after an acute myocardial infarction.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133052520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-04DOI: 10.3390/MOL2NET-05-06237
Maria Galeana Rojas
Cancer is the leading cause of death worldwide, affecting child’s and adults, poor and rich, female and male. Between 30% and 50% of cancers type can be prevent with healthy lifestyle. On 2015, 8,8 million people died of cancer, this the 16% of world habitants. The economy impact of cancer is significant and still increasing. It is estimated that the total cost of cancer in 2010 was approximately of 1.16 billion dollars. Only one of five medium and low-income countries have necessary data to combat this illness. Nowadays, scientists are betting on herbal medicine for cancer and they are searching good results on this ancient’s treatments, increasing life expectancy of the patients.
{"title":"Medicinal plants extract for cancer treatment","authors":"Maria Galeana Rojas","doi":"10.3390/MOL2NET-05-06237","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06237","url":null,"abstract":"Cancer is the leading cause of death worldwide, affecting child’s and adults, poor and rich, female and male. Between 30% and 50% of cancers type can be prevent with healthy lifestyle. On 2015, 8,8 million people died of cancer, this the 16% of world habitants. The economy impact of cancer is significant and still increasing. It is estimated that the total cost of cancer in 2010 was approximately of 1.16 billion dollars. Only one of five medium and low-income countries have necessary data to combat this illness. Nowadays, scientists are betting on herbal medicine for cancer and they are searching good results on this ancient’s treatments, increasing life expectancy of the patients.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"22 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121006330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-04DOI: 10.3390/MOL2NET-05-06236
Arely Paramo
Biolumiscence is the ability of some living beings to produce light thanks to chemical reactions in these organisms. The bioluminescence of fireflies has been used as an important tool (analytical techniques) within various studio fields. Luciferin (substrate for providing bioluminescence) is encoded by specific DNA sequences. Thanks to genetic engineering these sequences have been copied in such a way that they can be used in tissues for research purposes or for purposes such as cancer treatment. This article will talk about how light is formed from fireflies and how it is used in various applications.
{"title":"Luciferase as a research technique for biological processes","authors":"Arely Paramo","doi":"10.3390/MOL2NET-05-06236","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06236","url":null,"abstract":"Biolumiscence is the ability of some living beings to produce light thanks to chemical reactions in these organisms. The bioluminescence of fireflies has been used as an important tool (analytical techniques) within various studio fields. Luciferin (substrate for providing bioluminescence) is encoded by specific DNA sequences. Thanks to genetic engineering these sequences have been copied in such a way that they can be used in tissues for research purposes or for purposes such as cancer treatment. This article will talk about how light is formed from fireflies and how it is used in various applications.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"86 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120841693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-04DOI: 10.3390/MOL2NET-05-06238
L. Jauregui
Alzheimer´s Disease (AD) is a neurodegenerative disorder which represents a problem for the public health system because it affects more than 50 million people in the world, currently there is no successful treatment to treat this disease. The most accepted hypothesis regarding the development of this disease is the accumulation of plaques Aβ in the brain, have studied different molecules of natural origin as treatment based on this hypothesis. Cannabis sativa L. is a plant that has great potential as a treatment for this disease due to its antioxidant and neuroprotective properties and it has been shown to reduce the accumulation of Aβ plaques.
{"title":"Use of Cannabis sativa L. for the treatment of Alzheimer's disease","authors":"L. Jauregui","doi":"10.3390/MOL2NET-05-06238","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06238","url":null,"abstract":"Alzheimer´s Disease (AD) is a neurodegenerative disorder which represents a problem for the public health system because it affects more than 50 million people in the world, currently there is no successful treatment to treat this disease. The most accepted hypothesis regarding the development of this disease is the accumulation of plaques Aβ in the brain, have studied different molecules of natural origin as treatment based on this hypothesis. Cannabis sativa L. is a plant that has great potential as a treatment for this disease due to its antioxidant and neuroprotective properties and it has been shown to reduce the accumulation of Aβ plaques.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127160032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-03DOI: 10.3390/MOL2NET-05-06234
L. Cornejo
Alzheimer's Disease is considered a multifactorial and really complex disorder. Pathological mechanisms in this illness are not completely identified and actual drugs have poor effects on disease's progression. Consequently, multi-target therapeutic turns attractive in the way to find new drug options. As a result of their antioxidant and anti-inflammatory benefits add to their regulation effects in signal transduction, apoptosis pathways, and cellular differentiation, polyphenols have an enormous value as chemoprotectors in SNC diseases. Resveratrol has multiple anti-AD effects including anti-inflammatory and anti-oxidant actions in neurodegeneration disorders, reduction of Aβ production and deposition, reduction of hyper phosphorylation of tau protein, regulation of mi RNA a gene translation, modulation of estrogen-dependent receptors, regulation of cell autophagy and neurotransmissor toxicity. Despite the pharmacokinetic challenges, resveratrol is a potential drug for a multi-target therapy model.
{"title":"Resveratrol as a possible multitarget drug for Alzheimer's Disease","authors":"L. Cornejo","doi":"10.3390/MOL2NET-05-06234","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06234","url":null,"abstract":"Alzheimer's Disease is considered a multifactorial and really complex disorder. Pathological mechanisms in this illness are not completely identified and actual drugs have poor effects on disease's progression. Consequently, multi-target therapeutic turns attractive in the way to find new drug options. As a result of their antioxidant and anti-inflammatory benefits add to their regulation effects in signal transduction, apoptosis pathways, and cellular differentiation, polyphenols have an enormous value as chemoprotectors in SNC diseases. Resveratrol has multiple anti-AD effects including anti-inflammatory and anti-oxidant actions in neurodegeneration disorders, reduction of Aβ production and deposition, reduction of hyper phosphorylation of tau protein, regulation of mi RNA a gene translation, modulation of estrogen-dependent receptors, regulation of cell autophagy and neurotransmissor toxicity. Despite the pharmacokinetic challenges, resveratrol is a potential drug for a multi-target therapy model.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"12 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134466437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-03DOI: 10.3390/MOL2NET-05-06235
Alma Delia Luna Gonzalez
HCN channels play a variety of important functions in our body, this can be from the control in the heart rate as in the central and peripheral nervous system. This type of channel is voltage dependent and has a permeability to Na+ and K+, this permeability is usually controlled by the cAMP that is inside the cell. HCN channels participate in human diseases such as pain, heart failure, etc., and having a fundamental role in our body functions can offer new tools that allow the pharmaceutical industry to develop drugs, mainly analgesics.
{"title":"Importance of HCN channels involved in various body conditions","authors":"Alma Delia Luna Gonzalez","doi":"10.3390/MOL2NET-05-06235","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06235","url":null,"abstract":"HCN channels play a variety of important functions in our body, this can be from the control in the heart rate as in the central and peripheral nervous system. This type of channel is voltage dependent and has a permeability to Na+ and K+, this permeability is usually controlled by the cAMP that is inside the cell. HCN channels participate in human diseases such as pain, heart failure, etc., and having a fundamental role in our body functions can offer new tools that allow the pharmaceutical industry to develop drugs, mainly analgesics.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"330 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115016645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-14DOI: 10.3390/MOL2NET-05-06231
R. Kachhap, Amitesh Gupta, Rajarshi Bhattacharjee, Triparna Sett
Seismic risk assessment in the high mountains of Himalaya is necessary toaccommodate safe and suitable sites for homing with also to direct the pathway of plan and policyfor development sustainably. The continuous orogeny results often earthquakes, mostly, the areaaround fault lines as have been documented by USGS. Hence, to prepare the vulnerability andsusceptible zonation in East and South Sikkim districts Analytical Hierarchy Process (AHP)technique has been adopted. LANDSAT 8 onboard OLI multispectral data is used to prepare theLand-use Land-cover map of study area using supervised classification techniques, whileCartoSAT-1 version 2 DEM is used to look into the physiographical aspects of this region. Withalso, Geological Survey of India prepared soil and geological map is used to prepare the soil andlineament map. Not only that, ground motion data of four different parameters, have also beenacquired form USGS on about of an earthquake event on 18th September 2011, which hadepicenter at 27.730°N, 88.155°E. Certainly, it has been achieved that, area with soil type ofudorthents entisol in the 10 km buffer zone from the major faults victimized of seismic hazardmostly. By the AHP comparison matrix, proximity of any area to the fault lines found to be mostinfluential followed by the ground motion vectors while the LULC categories are the leastinfluential. Using the weighted overlay analysis, area along the western boundary of East districtand north-west of South district in Sikkim found to be under high seismic risk zone. Risk zones hasbeen verified with the help of archive earthquake data from USGS and approximately 22% area inthese two districts comes under high risk zone.
在喜马拉雅高山区进行地震风险评估是必要的，它可以为人类提供安全适宜的家园，并指导可持续发展的规划和政策路径。根据美国地质勘探局的记录，持续的造山运动经常导致地震，主要是在断层线附近地区。因此，采用层次分析法(AHP)编制了锡金东部和南部地区的脆弱性和易感区划。利用LANDSAT 8机载OLI多光谱数据，利用监督分类技术编制研究区域的land -use land -覆被图，同时利用cartosat -1版本2 DEM研究该区域的地理特征。此外，还使用印度地质调查局编制的土壤和地质图来编制土壤和地貌图。不仅如此，我们还从美国地质勘探局获得了2011年9月18日发生在北纬27.730°，东经88.155°的一次地震的4个不同参数的地震动数据。可以肯定的是，在距主要断层10 km的缓冲带内，具有牙体土类型的地区最容易发生地震灾害。通过AHP比较矩阵，发现任何区域与断层线的接近程度影响最大，其次是地面运动矢量，而LULC类别影响最小。通过加权叠加分析，发现锡金东部地区西部边界和南部地区西北部地区处于地震高危险区。在美国地质勘探局地震档案数据的帮助下，已经对危险区域进行了验证，这两个地区大约22%的面积属于高风险区域。
{"title":"Seismic risk zonation using the geospatial tool: A case study over East and South district of Sikkim","authors":"R. Kachhap, Amitesh Gupta, Rajarshi Bhattacharjee, Triparna Sett","doi":"10.3390/MOL2NET-05-06231","DOIUrl":"https://doi.org/10.3390/MOL2NET-05-06231","url":null,"abstract":"Seismic risk assessment in the high mountains of Himalaya is necessary toaccommodate safe and suitable sites for homing with also to direct the pathway of plan and policyfor development sustainably. The continuous orogeny results often earthquakes, mostly, the areaaround fault lines as have been documented by USGS. Hence, to prepare the vulnerability andsusceptible zonation in East and South Sikkim districts Analytical Hierarchy Process (AHP)technique has been adopted. LANDSAT 8 onboard OLI multispectral data is used to prepare theLand-use Land-cover map of study area using supervised classification techniques, whileCartoSAT-1 version 2 DEM is used to look into the physiographical aspects of this region. Withalso, Geological Survey of India prepared soil and geological map is used to prepare the soil andlineament map. Not only that, ground motion data of four different parameters, have also beenacquired form USGS on about of an earthquake event on 18th September 2011, which hadepicenter at 27.730°N, 88.155°E. Certainly, it has been achieved that, area with soil type ofudorthents entisol in the 10 km buffer zone from the major faults victimized of seismic hazardmostly. By the AHP comparison matrix, proximity of any area to the fault lines found to be mostinfluential followed by the ground motion vectors while the LULC categories are the leastinfluential. Using the weighted overlay analysis, area along the western boundary of East districtand north-west of South district in Sikkim found to be under high seismic risk zone. Risk zones hasbeen verified with the help of archive earthquake data from USGS and approximately 22% area inthese two districts comes under high risk zone.","PeriodicalId":337320,"journal":{"name":"Proceedings of MOL2NET 2019, International Conference on Multidisciplinary Sciences, 5th edition","volume":"61 23","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114052388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-05-22DOI: 10.3390/MOL2NET-05-06180
Akanksha Limaye, Anuraj Nayarisseri
Background Tay Sachs is a very rare neurodegenerative disorder and the second most common lipid storage disorder. The testimony of TSD in infants is marked by the gradual loss in vision, hearing impairment, increased muscle stiffness and cherry red retinal spot. These symptoms progress to paralysis, dementia, seizures, neuro-regression leading to the demise of the patient by the age of 3 to 4 years of age. The neurological and visceral accumulation of glycosphingolipids accounts for the major morbidity and mortality of the patients [1]. Tay Sachs disorder (TSD) is characterised by the accumulation of the ganglioside in the brain nerve cells. The abnormal accumulation of the shpingolipids (GalNAc-&1,4-(NeuNAc-&2,3) -Gal+1,4-Glc_13-1,1{2-N-acyl) sphingosine and GalNAc-/3-1,4-Gal_P1,4- GlcQ- 1,1(2-N-acyl)sphingosine) in nerve tissue leads to progressive dysfunction of the central nervous system [2]. When the enzyme 3-N-acetyl hexosaminidase (hexosaminidase A (HEXA)) is responsible for the breakdown of the fats- are defective, the glycosphingolipids increase excessively.[3] The HEXA gene, responsible for coding of the hexosaminidase A, is located on Chromosome 15. Currently, there are no promising cure for TSD as the treatment targets the symptoms of the disease [4]. The advanced techniques have introduced CRISPR/cas9 as the suggestive treatment plan. NGS (next generation sequencing) is one such diagnostic tool- providing rapid and accurate genomic information of the patient. The speculation of CRISPR/Cas9 requires critical understanding of the key genes involved, in order to design the treatment plan. The CRISPR (clustered regularly interspaced repeats) technology allows scientists to make the precise change in the genetic code. Cas9 endonucleases is the associated protein which is guided through specifically designed guide-RNA to the target DNA. CRISPR/Cas9 selectively target genes containing mutations that lead to non-functional products and correct the disease-causing mutations, in vitro and in vivo [5]. Currently the platforms used for gene editing for TSD patients include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and endonucleases. But these alternative platforms fail to provide ease and diversity in the areas where the CRISPR/cas9 excels. Owing to its ability to manipulate the target genes, however, the efficacy of the single guided RNA can be challenged, resulting in the unintended cleaving of the non-target sites. Thus, with the framework of the machine learning, using the algorithm of CRISTA the propensity of the cleaving the target site can be determined easily. The advanced techniques of machine learning along with NGS, provide varied scope of precise qualitative and quantitative study of the disorder. The suggested research work holds promising and revolutionary grounds in designing the treatment plan for the patient. The precise treatment can be planned on the basis of early diagnosis of
Tay Sachs是一种非常罕见的神经退行性疾病，也是第二常见的脂质储存疾病。婴儿创伤后应激障碍的症状表现为视力逐渐丧失，听力受损，肌肉僵硬增加，视网膜出现樱桃红色斑点。这些症状发展为瘫痪、痴呆、癫痫发作、神经退化，导致患者在3至4岁时死亡。神经和内脏鞘糖脂的积累是患者发病和死亡的主要原因[1]。Tay Sachs障碍(TSD)的特征是神经节苷脂在脑神经细胞中的积累。神经组织中鞘脂(GalNAc-&1,4-(NeuNAc-&2,3) - gal +1,4- glc_13 -1,1{2- n -酰基)鞘脂和GalNAc-/ 3,1,4 - gal_p1,4- GlcQ- 1,1(2- n -酰基)鞘脂)的异常积累可导致中枢神经系统进行性功能障碍[2]。当负责分解脂肪的3- n -乙酰己糖氨基酶(己糖氨基酶A (HEXA))出现缺陷时，鞘糖脂会过度增加。[3]负责编码己糖氨酸酶A的HEXA基因位于第15号染色体上。目前，由于治疗的目标是疾病的症状，没有希望治愈创伤后应激障碍[4]。先进的技术已经引入了CRISPR/cas9作为提示治疗方案。NGS(下一代测序)就是这样一种诊断工具——提供快速和准确的患者基因组信息。对CRISPR/Cas9的推测需要对所涉及的关键基因进行批判性的理解，以便设计治疗方案。CRISPR技术允许科学家对遗传密码进行精确的改变。Cas9核酸内切酶是一种相关蛋白，它通过专门设计的引导rna被引导到目标DNA。在体外和体内，CRISPR/Cas9选择性地靶向含有导致无功能产物的突变的基因，并纠正致病突变[5]。目前用于TSD患者基因编辑的平台包括锌指核酸酶(ZFNs)、转录激活因子样效应核酸酶(TALENs)和核酸内切酶。但是这些替代平台无法在CRISPR/cas9擅长的领域提供易用性和多样性。然而，由于其操纵靶基因的能力，单导RNA的功效可能受到挑战，导致非靶位点的意外切割。因此，在机器学习的框架下，使用CRISTA算法可以很容易地确定切割目标位点的倾向。先进的机器学习技术以及NGS，为这种疾病提供了各种范围的精确定性和定量研究。建议的研究工作在为患者设计治疗方案方面具有前景和革命性的基础。可以在疾病的早期诊断的基础上制定精确的治疗方案。机器学习技术在这一领域的发展可以保证一个明确的神经治疗方法，因为模型可以预测疾病的精确进展。这项提议的工作不仅提供了Tay Sachs领域的研究，而且对阿尔茨海默氏症、痴呆症、亨廷顿舞蹈症等神经退行性疾病的治疗仍是科学家们的谜题。参考文献:Khera, D, John, J.， Singh, K.， & Faruq, M.(2018)。泰-萨克斯病:一种来自印度的新突变。中华医学会病例报告，11(1)，e225916。Sandhoff, K. (1969). doi:10.1136/bcr-2018-225916Tay - Sachs病中β - N -乙酰己糖氨酸酶模式的变化FEBS letters, 4(4)， 351-354。(1998)。中国药理学杂志，26(4)，421 - 421。Kaback, M. (1993). doi:10.1016/s0006-2952(98)。泰-萨克斯病-携带者筛选，产前诊断，和分子时代。中国生物医学工程杂志，2011(3)，391 - 391。Christensen, C.， & Choy, F.(2017)。溶酶体贮积病的前瞻性治疗选择:用于诱导多能干细胞突变校正的CRISPR/Cas9基因编辑技术疾病杂志，5(1)，6。
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Pub Date : 2019-05-15DOI: 10.3390/MOL2NET-05-06179
Anuraj Nayarisseri, Trishang Udhwani
Hemophilia can be defined as a genetic disorder in which the body loses its capability to clot blood, and hence can’t stop blood flow. It is an X- linked recessive disease, hence mostly seen in males, with its severity significantly reduced in females. In India, hemophilia has an occurrence of 1 per 10,000 births, which generally progresses to a chronic disability or premature death in subjects left untreated or provided with suboptimal treatment, a case prevalent in India [1]. The two major types of this condition are hemophilia A or factor VIII deficiency and hemophilia B or factor IX deficiency. In addition, hemophilia C is a rare category in which inhibitory antibodies develop which show high affinity to procoagulants, thus neutralizing the effect of a coagulation factor. Inhibitors are much less common in patients with hemophilia B than in those with hemophilia A. The F8 gene present on the X chromosome is responsible for guiding the production of coagulation factor VIII, essential for forming blood clots. In hemophilia A, mutation results from two gross (140 kbp or 600 kbp) chromosomal inversions that involve introns 1 and 22, respectively. Similarly, the F9 gene present on the X chromosome mutates through several different mechanisms to give rise to hemophilia B condition. The conditions associated with hemophilia Leyden, ribosome readthrough of nonsense mutation and apparently ‘silent’ changes that do not alter amino acids are the major mutations studied. It has been observed that reconstitution with 1–2% of the clotting factor helps uplift the quality of life, while 5–20% reconstitution is required to ameliorate the genetic disorder. Gene-specific genome editing is preferred over random integration of expression cassettes as this helps avoid genotoxicity and achieve the required physiological levels of expression. Advances in genome engineering based on CRISPR- associated RNA- guided endonuclease Cas9 are empowering the guidance of the said endonuclease to target locations by a short RNA search string [2]. It requires a programmable sequence-specific RNA to direct it and introduce cleavage and double-stranded breaks at the target site. In case of hemophilia A, induced pluripotent stem cells (iPSCs) can be derived from patients with inversion genotypes with an aim to revert these chromosomal conditions to the corrected state with the assistance of CRISPR- Cas9 nucleases [3]. The endothelial cells from the corrected iPSCs can be checked for expression of F8 gene and the production of factor VIII. Likewise, in case of hemophilia B, delivery of naked Cas9-sgRNA plasmid and donor DNA, aiming to recover the mutation has shown a detectable gene correction (>1%) in F9 alleles of hepatocytes [4]. To construct the related plasmids, an AAVS1-Cas9-sgRNA plasmid is designed to cut the AAVSI locus in human. Subsequently, two donor plasmids are designed to insert GFP and F9 cDNA into the designated AAVS1 locus. Whole genome sequencing (WGS) is used in
血友病可以被定义为一种遗传性疾病，其中身体失去了凝血能力，因此无法阻止血液流动。它是一种X连锁隐性疾病，因此多见于男性，其严重程度在女性中显著降低。在印度，血友病的发病率为万分之一，如果不及时治疗或治疗不理想，血友病通常会发展为慢性残疾或过早死亡，这种情况在印度非常普遍。这种情况的两种主要类型是血友病A或因子VIII缺乏症和血友病B或因子IX缺乏症。此外，C型血友病是一种罕见的类型，其中抑制抗体的产生对促凝剂表现出高亲和力，从而中和凝血因子的作用。抑制剂在B型血友病患者中比在a型血友病患者中少得多。存在于X染色体上的F8基因负责指导凝血因子VIII的产生，凝血因子VIII是形成血凝块所必需的。在A型血友病中，突变由两个总(140 kbp或600 kbp)染色体倒位引起，分别涉及内含子1和22。同样，存在于X染色体上的F9基因通过几种不同的机制发生突变，从而导致血友病B。与莱登血友病相关的条件，核糖体无义突变的解读，以及明显的“沉默”变化，不改变氨基酸是研究的主要突变。据观察，1-2%的凝血因子重组有助于提高生活质量，而5-20%的重组需要改善遗传疾病。基因特异性基因组编辑优于随机整合表达磁带，因为这有助于避免遗传毒性并达到所需的生理表达水平。基于CRISPR相关RNA引导的核酸内切酶Cas9的基因组工程进展，使所述核酸内切酶能够通过短RNA搜索串[2]引导到目标位置。它需要一个可编程的序列特异性RNA来指导它，并在目标位点引入切割和双链断裂。对于A型血友病，诱导多能干细胞(iPSCs)可以从基因型倒置的患者中获得，目的是在CRISPR- Cas9核酸酶[3]的帮助下将这些染色体状况恢复到正确状态。校正后的iPSCs内皮细胞可以检测F8基因的表达和因子VIII的产生。同样，在B型血友病中，为了恢复突变，将裸Cas9-sgRNA质粒和供体DNA传递给肝细胞[4]的F9等位基因，显示出可检测到的基因校正(>1%)。为了构建相关质粒，我们设计了AAVS1-Cas9-sgRNA质粒来切割人AAVSI基因座。随后，设计两个供体质粒，将GFP和F9 cDNA插入指定的AAVS1位点。全基因组测序(WGS)与这种编辑方法相结合，用于识别脱靶突变，以确保在所需的位点进行编辑。与常用的腺相关病毒(AAV)载体相比，该技术具有精度、减少插入性肿瘤发生和通过内源性启动子[5]控制等优点。CRISPR/Cas9介导的AAV8载体基因组编辑已被用于提供可调节的路径，以诱导肝细胞[6]靶基因的双链断裂。CRISPR-Cas9的首要需求是鉴定发生突变的靶标，这导致了上述疾病的发展。虽然已知一些靶标，但没有一个靶标突变能够实现消除这种疾病所需的5- 20%的重组。因此，有必要为CRISPR-Cas9系统寻找新的靶点，这反过来又需要计算工具的帮助。本研究的目的是确定阳性的CRISPR-Cas9靶点，这将有助于更好，更准确地治疗疾病，计算生物学促进研究。该研究提供了具有最小脱靶突变的靶标，为血友病提供了最大的重建。参考文献[10]Kar, A, Phadnis, S, Dharmarajan, S, and Nakade, J.(2014)。印度血友病的流行病学和社会成本。《印度医学研究杂志》，140(1)，第19页。[2], p D。兰德,e·S。&张f(2014)。CRISPR-Cas9在基因组工程中的发展与应用Cell, 157(6)， 1262-1278。[3], c . Y。金,d·H。儿子,J·S。唱,J . J。李,J。,Bae, S。,……& Kim J. S.(2015)。使用CRISPR-Cas9对血友病A患者来源的iPSCs中大因子VIII基因染色体倒位的功能校正细胞干细胞，17(2)，213-220。[4]淮河、C。,C,太阳,R,徐,P, Min, T, Wang Q。,……&卢D.(2017)。
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