E-cadherin gene C-160A promoter polymorphism and risk of non-cardia gastric cancer in a Chinese population

AIM: To test the hypothesis that E-cadherin gene (CDH1)C-160A promoter variant genotype is associated with an increased risk for developing gastric cancer.METHODS: In this population-based case-control study of gastric cancer in Jiangsu Province, China, we performed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the C-160A polymorphism of CDH1 promoter in 206 non-cardia gastriccancer patients and 261 age- and sex-matched but unrelated cancer-free controls.RESULTS: The frequencies of genotypes CC, CA and AA were 57.8%, 36.4% and 5.8% in gasfric cancer cases,respectively, and 58.2%, 34.9% and 6.9% in controls respectively. The distributions of CDH1 genotypes were not significantly different between gastric cancer cases and controls (P = 0.87 for genotype frequency and P = 0.92for allele frequency). Compared with the CC genotype, the CA and AA genotypes were not associated with an increased risk for non-cardia gastric cancer (adjusted odds ratios (OR)= 1.15, and 95% confidence interval (95% CI) = 0.78-1.72for CA genotype, and OR = 0.90 and 95% CI = 0.42-2.01for AA genotype).CONCLUSION: E-cadherin gene C-160A promoter polymorphism may not play a major role in the etiology of non-cardia gastric cancer in Chinese population.

No association exists between E-cadherin gene polymorphism and tumor recurrence in patients with hepatocellular carcinoma after transplantation

BACKGROUND: E-cadherin is an epithelial cell adhesion molecule, and decreased E-cadherin expression in liver cancer is associated with poor prognosis. A -160 C -> A polymorphism in the promoter region of E-cadherin has been reported to decrease gene transcription. This allelic variation may be a potential genetic marker for identifying those individuals at higher risk for invasive/metastatic disease. METHODS: The effect of E-cadherin gene polymorphism on risk of tumor recurrence was studied in 93 patients with hepatocellular carcinoma (HCC) after liver transplantation, and determined whether this polymorphism is a biomarker for the risk of tumor recurrence. RESULTS: The genotype frequencies in the patients with recurrence were C/C: 0.667, C/A: 0.311, and A/A: 0.022, and in-the patients without recurrence C/C: 0.604, C/A: 0.271 and A/A: 0.125. No significant difference was found between the two groups (P = 0.171). Between -160 C -> A polymorphism and the clinicopathological data, there were no statistically significant differences in the distribution of the parameters as to age, gender, portal vein tumor thrombi, preoperative alpha-fetoprotein level, tumor size, or histopathological grading (P > 0.05). CONCLUSION: The results of this study show no association exists between the E-cadherin genotype and the risk of tumor recurrence in Chinese patients with HCC.

miR-200c/ZEB1/E-cadherin轴在胆管癌转移侵袭中的作用及对胆管癌预后评估的价值

目的:探讨微小RNA-200c(miR-200c)/锌指转录因子(ZEB1)/E-钙黏蛋白(E-cadherin)在胆管癌(HCCA)转移、侵袭中的作用及对HCCA预后评估的临床价值。方法:选取2020年08月至2022年12月间我院收治的胆管癌患者36例为研究对象,同时选取胆管良性疾病患者(胆总管结石或胆管良性狭窄)20例作为对照。采用原位杂交、实时荧光定量PCR检测miR-200c在HCCA患者组织及血清中的表达;生存曲线分析miR-200c表达与总生存期的相关性;Transwell实验检测细胞的迁移及侵袭能力;免疫印迹检测ZEB1及E-cadherin蛋白的表达。体内研究构建裸鼠成瘤实验,采用免疫组化检测ZEB1及E-cadherin蛋白的表达;Tunel技术检测组织中的凋亡情况。受试者工作特征(ROC)曲线评估生物标志物对胆管癌预后的诊断效能。结果:miR-200c低表达于HCCA组织及血清中;生存曲线分析显示,miR-200c表达与患者的总生存期呈正相关性,TNM分期与患者的总生存期呈负相关性;miR-200c mimics抑制了胆管癌细胞的迁移和侵袭能力,并降低ZEB1表达而诱导E-cadherin表达;转染ZEB1逆转miR-200c的作用效应,促进胆管癌细胞的迁移和侵袭特性,抑制胆管癌细胞的凋亡。CA199、CEA和miR-200c联合检测诊断胆管癌预后的ROC曲线下面积为0.892,灵敏度0.8611,特异度0.8000。结论:miR-200c/ZEB1/Ecadherin轴参与胆管癌的转移侵袭;CA199、CEA和miR-200c联合检测对胆管癌预后的诊断效能良好,对临床胆管癌的治疗策略具有重要指导价值。

芪贞归脾汤辅助治疗对食管癌伴锁骨上淋巴结转移患者细胞E-cadherin表达的影响

目的探讨芪贞归脾汤辅助治疗对食管癌伴锁骨上淋巴结转移患者细胞钙黏素(E-cadherin)表达的影响。方法选取2016年1月—2021年1月食管癌伴锁骨上淋巴结转移病例96例,随机编号方法分两组,各48例,对照组采用常规放疗;在此基础上,观察组采用芪贞归脾汤辅助治疗,持续治疗8周。治疗前后评价中医证候积分、匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)、免疫功能、细胞角蛋白19片段(cytokeratin 19 fragment,CYFRA21-1)、癌胚抗原(carcinoembryonic antigen,CEA)、癌抗原(cancer antigen 125,CA125)、E-cadherin和不良反应情况。结果观察组治疗后咽下困难、胸闷不舒、形体消瘦、气短乏力等积分低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后睡眠质量、入睡时间、睡眠时间、睡眠效率、睡眠障碍、催眠药物、日间功能障碍等评分低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后CD^(+)_(3)、CD^(+)_(4)、CD^(+)_(4)/CD^(+)_(8)高于对照组,CD^(+)_(8)低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后血清CYFRA21-1、CEA、CA125低于对照组,差异有统计学意义(均P<0.05)。观察组治疗后E-cadherin阳性率72.92%高于对照组54.17%,差异有统计学意义(P<0.05)。两组放射性皮炎、恶心呕吐、白细胞减少、肝功能异常、神经毒性等不良反应比较,差异无统计学意义(均P>0.05)。结论芪贞归脾汤辅助治疗可以提高食管癌伴锁骨上淋巴结转移患者的免疫功能和睡眠质量,降低肿瘤标志物及E-cadherin的表达,安全性高。

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

卵巢浆液性癌中miR-182和E-cadherin的表达及意义

目的检测卵巢浆液性癌中微小RNA-182(microRNA-182,miR-182)和上皮型粘附素(E-cadherin)的表达,探讨其相关性及临床意义。方法选择行卵巢浆液性癌根治性手术的患者59例作为研究组,选择行手术治疗的卵巢浆液性囊腺瘤患者59例作为对照组,应用实时荧光定量PCR法检测组织中miR-182的表达,应用免疫组化法检测组织E-cadherin的表达。结果研究组中miR-182的表达量(1.83±0.32)明显高于对照组(1.31±0.31)(t=4.59,P=0.012),研究组中E-cadherin表达阳性率(47.46%)明显低于对照组(84.75%)(X~2=18.31,P=0.000)。miR-182和E-cadherin在卵巢浆液性癌不同级别(2.01±0.29 vs.1.66±0.22)(27.59%vs.66.67%)、不同肿瘤最大径(1.93±0.22 vs.1.64±0.39)(28.21%vs.85.00%)及有无脉管癌栓(1.80±0.15 vs.2.03±0.20)(20.00%vs.53.06%)的比较中差异有统计学意义(P<0.05),而在不同年龄、有无淋巴结转移分组的比较中差别无统计学意义(P>0.05)。线性相关分析显示研究组中miR-182与E-cadherin呈负相关性(r=-0.57,P=0.008)。生存分析显示miR-182的表达与患者生存时间有关(P<0.05)。结论miR-182和E-cadherin在卵巢浆液性癌中异常表达且具有相关性,组织中miR-182高表达提示不良预后。

AMME chromosomal region gene 1基因变异矮小相关综合征一例及文献复习

目的探讨1例身材矮小、面中部发育不全患儿的病因,以提高临床医师对特殊矮小综合征的认识。方法收集1例身材矮小、面中部发育不全患儿的临床资料,对患儿及父母行基因检测,并给予患儿常规治疗、随访。结果结合患儿特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征,结合文献复习总结AMMECR1基因变异矮小相关综合征特点。结论AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,临床主要表现为身材矮小、运动语言落后、肌张力减低、听力损失、面中部发育不全,部分存在心脏改变、腭裂、骨骼改变及椭圆形红细胞增多症、智力落后和肾钙质沉着症。该文报道1例AMMECR1基因新变异引起身材矮小、面中部发育不全患儿的病例资料,结合特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征。AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,本文初步概括其特点,并结合文献进行分析,以提高临床医师对AMMECR1基因变异矮小相关综合征的诊治。

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

卵巢肿瘤患者血清E-cadherin、CK19表达与病理特征的相关性

目的探讨卵巢肿瘤患者血清E-cadherin、CK19表达与病理特征的相关性。方法将88例接受根治性手术治疗的卵巢肿瘤患者设为卵巢肿瘤组,选择同期在本院体检的88名健康人群为正常组。检测卵巢肿瘤组与对照组的E-cadherin、CK19表达表达水平,调查卵巢肿瘤患者的病理特征、预后并进行相关性分析。结果卵巢肿瘤组的血清E-cadherin、CK19含量均显著高于对照组,差异有统计学意义(P<0.05)。卵巢肿瘤患者中,淋巴结转移19例、鳞癌48例、腺癌40例;Ⅰ期50例、Ⅱ期38例;高分化38例、中分化28例,低分化22例。Spearsman相关分析显示,患者的临床分期、组织学分化、淋巴结转移、肿瘤最大直径与血清E-cadherin、CK19含量均存在相关性,差异有统计学意义(P<0.05)。多因素Cox比例风险模型分析显示,血清E-cadherin、CK19含量都为影响患者预后中位生存时间的重要因素,差异有统计学意义(P<0.05)。结论卵巢肿瘤患者多伴随有血清E-cadherin、CK19的高表达,血清E-cadherin、CK19表达水平与病理特征存在相关性,也是影响患者预后的重要危险因素。

Biotin-modified Galactosylated Chitosan-gene Carrier in Hepatoma Cells Targeting Delivery

Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1.At this N/P ratio,the transfection efficiency in the hepatoma cells was the highest with a slow release effect.Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation,and can target the transfection into hepatoma cells by combination with galactose and biotin receptors.The transfection rate was inhibited by the competition of galactose and biotin.Bio-GC nanomaterials were imported into cells’cytoplasm by their receptors,followed by the imported exogenous gene transfected into the cells.Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice,by carrying the gene through the blood to the hepatoma tissue.Taken together,bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation,improving the rate of transfection in hepatoma cells,and transporting the gene into the cytoplasm in vitro and in vivo.Therefore,they are efficient hepatoma-targeting gene carriers.

Decoding Retinoblastoma: Differential Gene Expression

Background: Retinoblastoma, the most common intraocular pediatric cancer, presents complexities in its genetic landscape that necessitate a deeper understanding for improved therapeutic interventions. This study leverages computational tools to dissect the differential gene expression profiles in retinoblastoma. Methods: Employing an in silico approach, we analyzed gene expression data from public repositories by applying rigorous statistical models, including limma and de seq 2, for identifying differentially expressed genes DEGs. Our findings were validated through cross-referencing with independent datasets and existing literature. We further employed functional annotation and pathway analysis to elucidate the biological significance of these DEGs. Results: Our computational analysis confirmed the dysregulation of key retinoblastoma-associated genes. In comparison to normal retinal tissue, RB1 exhibited a 2.5-fold increase in expression (adjusted p Conclusions: Our analysis reinforces the critical genetic alterations known in retinoblastoma and unveils new avenues for research into the disease’s molecular basis. The discovery of chemoresistance markers and immune-related genes opens potential pathways for personalized treatment strategies. The study’s outcomes emphasize the power of in silico analyses in unraveling complex cancer genomics.

GST family genes in jujube actively respond to phytoplasma infection

Jujube witches’broom(JWB)caused by phytoplasma has a severely negative effect on multiple metabolisms in jujube.The GST gene family in plants participates in the regulation of a variety of biotic and abiotic stresses.This study aims to identify and reveal the changes in the jujube GST gene family in response to phytoplasma infection.Here,70 ZjGSTs were identified in the jujube genome and divided into 8 classes.Among them,the Tau-class,including 44 genes,was the largest.Phylogenetic analysis indicated that Tau-class genes were highly conserved among species,such as Arabidopsis,cotton,chickpea,and rice.Through chromosome location analysis,37.1%of genes were clustered,and 8 of 9 gene clusters were composed of Tau class members.Through RT-PCR,qRT-PCR and enzyme activity detection,the results showed that the expression of half(20/40)of the tested ZjGSTs was inhibited by phytoplasma infection in field and tissue culture conditions,and GST activity was also significantly reduced.In the resistant and susceptible varieties under phytoplasma infection,ZjGSTU49-ZjGSTU54 in the cluster IV showed opposite expression patterns,which may be due to functional divergence during evolution.Some upregulated genes(ZjGSTU45,ZjGSTU49,ZjGSTU59,and ZjGSTU70)might be involved in the process of jujube against JWB.The yeast two-hybrid results showed that all 6 Tauclass proteins tested could form homodimers or heterodimers.Overall,the comprehensive analysis of the jujube GST gene family revealed that ZjGSTs responded actively to phytoplasma infection.Furthermore,some screened genes(ZjGSTU24,ZjGSTU49-52,ZjGSTU70,and ZjDHAR10)will contribute to further functional studies of jujube-phytoplasma interactions.

Genetic mechanism of body size variation in groupers:Insights from phylotranscriptomics

Animal body size variation is of particular interest in evolutionary biology,but the genetic basis remains largely unknown.Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size,providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates.Herein,we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea.Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size,respectively.A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups.Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups.These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks.Based on our results,we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection,leading to genetic variations in metabolic patterns,organ development,and lifespan,resulting in body size divergence between the two locally adapted populations.These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.

Fate and Behavior of Tetracycline Resistance Genes in Activated Carbon Adsorption

The accessibility of tetracycline resistance gene (tetG) into the pores of activated carbon (AC), as well as the impact of the pore size distribution (PSD) of AC on the uptake capacity of tetG, were investigated using eight types of AC (four coal-based and four wood-based). AC showed the capability to admit tetG and the average reduction of tetG for coal-based and wood-based ACs at the AC dose of 1 g·L-1 was 3.12 log and 3.65 log, respectively. The uptake kinetic analysis showed that the uptake of the gene followed the pseudo-second-order kinetics reaction, and the uptake rate constant for the coal-based and wood-based ACs was in the range of 5.97 × 10-12 - 4.64 × 10-9 and 7.02 × 10-11 - 1.59 × 10-8 copies·mg-1·min-1, respectively. The uptake capacity analysis by fitting the obtained experiment data with the Freundlich isotherm model indicated that the uptake constant (KF) values were 1.71 × 103 - 8.00 × 109 (copies·g-1)1-1/n for coal-based ACs and 7.00 × 108 - 3.00 × 1010 (copies·g-1)1-1/n for wood-based ones. In addition, the correlation analysis between KF values and pore volume as well as pore surface at different pore size regions of ACs showed that relatively higher positive correlation was found for pores of 50 - 100 Å, suggesting ACs with more pores in this size region can uptake more tetG. The findings of this study are valuable as reference for optimizing the adsorption process regarding antibiotic resistance-related concerns in drinking water treatment.

Effects of Heterologously Overexpressing PIP5K-Family Genes in Arabidopsis on Inflorescence Development

Castor is one of the top 10 oil crops in the world and has extremely valuable uses.Castor inflorescences directly affect yield,so the study of inflorescence development is very important in increasing castor yield.Our previous studies have shown that the PIP5K gene family(PIP5Ks)is associated with inflorescence development.In this study,to determine the function of each PIP5K gene in castor,a female Lm-type castor line,aLmAB2,was used to determine the relative expression levels of the PIP5Ks in castor inflorescences.Six PIP5K genes were heterologously overexpressed in Arabidopsis thaliana,the relative expression of each gene and the effect on plants was determined in A.thaliana,and the relationships among the PIP5Ks in castor were inferred.The expression levels of the PIP5Ks in the female Lm-type castor line aLmAB2 were analyzed.The relative expression levels of the PIP5K9 and PIP5K11 genes were high(p<0.05)in isofemale inflorescences,and those of PIP5K1,PIP5K2,PIP5K6,and PIP5K8 were high(p<0.05)in female inflorescences but low(p<0.05)in bisexual inflorescences.The PIP5Ks were heterologously overexpressed in A.thaliana,and T3-generation plants with stable genetic resistance,i.e.,AT-PIP5K^(+)plants(AT-PIP5K1^(+),AT-PIP5K2^(+),AT-PIP5K6^(+),AT-PIP5K8^(+),AT-PIP5K9^(+),and ATPIP5K11^(+) plants),were obtained.Biological tests of the AT-PIP5K+plants showed that the growth of the main stem was significantly delayed in AT-PIP5K+plants compared with Columbia wild-type(WT)A.thaliana plants;the PIP5K1 and PIP5K2 genes promoted lateral stem growth and flower and silique development;and the PIP5K6,PIP5K8,PIP5K9 and PIP5K11 genes inhibited lateral stem growth and flower and silique development.The correlations among PIP5Ks in castor suggest that there may be a synergistic relationship among PIP5K1,PIP5K2,and PIP5K6 in castor inflorescences,and PIP5K8,PIP5K9,and PIP5K11 are complementary to the other three genes.

The concept of gene therapy for glaucoma:the dream that has not come true yet

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent manner.The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model.Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

Increasingβ-hexosaminidase A activity using genetically modified mesenchymal stem cells

GM2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorde rs.These diseases result from a deficiency of lysosomal enzymeβ-hexosaminidase A(HexA),which is responsible for GM2 ganglioside degradation.HexA deficiency causes the accumulation of GM2-gangliosides mainly in the nervous system cells,leading to severe progressive neurodegeneration and neuroinflammation.To date,there is no treatment for these diseases.Cell-mediated gene therapy is considered a promising treatment for GM2 gangliosidoses.This study aimed to evaluate the ability of genetically modified mesenchymal stem cells(MSCs-HEXA-HEXB)to restore HexA deficiency in Tay-Sachs disease patient cells,as well as to analyze the functionality and biodistribution of MSCs in vivo.The effectiveness of HexA deficiency cross-correction was shown in mutant MSCs upon intera ction with MSCs-HEXA-HEXB.The results also showed that the MSCs-HEXA-HEXB express the functionally active HexA enzyme,detectable in vivo,and intravenous injection of the cells does not cause an immune response in animals.These data suggest that genetically modified mesenchymal stem cells have the potentials to treat GM2 gangliosidoses.