Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.

The organic geochemistry of crude oil in the Saltpond Basin(Ghana):Organic source input,depositional environment,and thermal maturity

The Saltpond Basin,situated within the South Atlantic margin of Ghana,is a significant area for petro-leum exploration but has received relatively limited research attention.Previous studies have examined source rock com-position,but data on crude oil organic chemistry are lack-ing,hindering understanding of the basin’s petroleum system and evolution.To address this gap,we analyzed biomarkers and stable carbon-isotope ratios in Saltpond Basin crude oil using gas chromatography–mass spectrometry and gas chromatography–isotope ratio mass spectrometry to eluci-date organic matter source,depositional environment,and thermal maturity.Findings were compared with oils from the West African segment of the South Atlantic margin,namely the Tano Basin and the Niger Delta Basin,to iden-tify potential correlations and gain insights into regional variations.Molecular and isotopic results unveiled a sig-nificant prevalence of organic matter derived from lower marine organisms.Patterns of organic matter deposition and preservation in Saltpond oil samples suggested a suboxic marine transitional environment,contradicting conventional understanding of terrestrial dominance in such settings.Moreover,the potential for degradation processes to obscure differentiation between terrestrial and marine organic mat-ter origins underscores the complex nature of organic mat-ter dynamics in transitional marine environments.Analysis of molecular thermal maturity indices suggested Saltpond oils were expelled from source rocks exhibiting thermal maturity at the early maturity stage.Correlation analysis unveiled genetic disparities among crude oils sourced from the Saltpond Basin and those from the Tano and Niger Delta Basin,primarily due to variations in source input and depo-sitional environment conditions.Saltpond oil exhibits lower terrestrial organic input than Tano Basin’s crude oils,which also have less terrestrial input than Niger Delta Basin crude oils.Additionally,its paleodepositional environment nota-bly differs from oils in the Tano Basin(anoxic transitional marine-lacustrine settings)and the Niger Delta Basin(sub-oxic–oxic terrigenous deltaic or marine or lacustrine envi-ronments).Thermal maturity range of Saltpond oil is com-parable to oils in the Tano Basin but lower than oils in the Niger Delta Basin.Thesefindings provide valuable insights into petroleum generation history and unique organic geo-chemical characteristics within the Saltpond Basin,essen-tial for exploration,production,and environmental manage-ment efforts in the region.Furthermore,correlation studies provide evidence that distinct biological,geological,and paleoenvironmental conditions shaped various oil types in the West African segment of the South Atlantic margin.

Geochemical fingerprints and hydrocarbon potential of Paleocene mudrocks in the Tano Basin, Ghana: insights from biomarkers and stable carbon isotopes

The Paleocene mudrocks in Ghana’s Tano Basin have received limited attention despite ongoing efforts to explore hydrocarbon resources.A thorough geochemical analysis is imperative to assess these mudrocks’petroleum generation potential and formulate effective exploration strategies.In this study,a comprehensive geochemical analysis was carried out on ten Paleocene rock cuttings extracted from TP-1,a discovery well within the Tano Basin.Various analytical techniques,including total organic carbon(TOC)analysis,Rock–Eval pyrolysis,gas chromatography-mass spectrometry,and isotope ratio-mass spectrometry,were employed to elucidate their hydrocar-bon potential and organic facies.Thefindings in this study were subsequently compared to existing geochemical data on Paleocene source rocks in the South Atlantic marginal basins.The results indicated that the Paleocene samples have TOC content ranging from 0.68 to 2.93 wt%.The prevalent kerogen types identified in these samples were Type Ⅱ and Type Ⅲ.Molecular and isotope data suggest that the organic matter found in the Paleocene mudrocks can be traced back to land plants and lower aquatic organisms.These mudrocks were deposited in a transi-tional environment withfluctuating water salinity,charac-terized by sub-oxic redox conditions.Maturity indices,both bulk and molecular,indicated a spectrum of maturity levels within the Paleocene mudrocks,spanning from immature to marginally mature,with increasing maturity observed with greater depth.In comparison,the organic composition and depositional environments of Paleocene source rocks in the Tano Basin closely resemble those found in the Niger Delta Basin,Douala,and Kribi-Campo Basins,the Kwanza Formation in Angola,and certain Brazilian marginal basins.However,it is worth noting that Paleocene source rocks in some of the basins,such as the Niger Delta and Brazilian marginal basins,exhibit rela-tively higher thermal maturity levels compared to those observed in the current Paleocene samples from the Tano Basin.In conclusion,the comprehensive geochemical analysis of Paleocene mudrocks within Ghana’s Tano Basin has unveiled their marginal hydrocarbon generation potential.The shared geochemical characteristics between the Paleocene mudrocks in the Tano Basin and those in the nearby South Atlantic marginal basins offer valuable insights into source rock quality,which is crucial for shaping future strategies in petroleum exploration in this region.

氯化咪唑基离子液体对柴油中含氮化合物选择性脱除作用研究

通过N-甲基咪唑和烷基氯的季铵化反应合成出了咪唑环N上烷基取代基碳链长度或者饱和度不同的4种离子液体:氯化1-丁基-3-甲基咪唑(BMImCl)、氯化1-烯丙基-3-甲基咪唑(AlMImCl)、氯化1-苯甲基-3-甲基咪唑(BzMImCl)和氯化-1-辛基-3-甲基咪唑(OcMImCl)。以含咔唑(CAR)和二苯并噻吩(DBT)的甲苯-正十二烷烃溶液作为模拟柴油,测定CAR和DBT在这些离子液体中的相对分配系数,考察了离子液体对氮和硫化物的萃取脱除选择性。结果表明,在这些离子液体中CAR比DBT有更高的分配系数;4种离子液体比较,BMImCl和AlMImCl对CAR的分配系数分别达46和14,对氮和硫化合物的萃取脱除选择性SN/S分别达到125和38。测定了离子液体在模拟柴油的溶解度,发现这4种离子液体在甲苯和正十二烷烃模拟柴油中的溶解度有显著的差别,其中BMImCl和AlMImCl的溶解度相当且都很小。综合结果显示BMImCl具有最佳性能。实验还比较了BMImCl对不同碱性氮杂环化合物的萃取效果,发现其对含硫化合物和碱性含氮化合物的萃取效率随着模拟柴油中甲苯的质量分数的增加而降低,而对中性含氮化合物表现出高萃取效率,且几乎不受甲苯质量分数的影响。对一种含有361 mg·kg-1N和3598 mg·kg-1S的工业柴油,BMImCl对其对中性含氮化合物的萃取效率达到38%,而对相对含量高约十倍的含硫化合物的萃取率仅约有1.7%。综合上述结果表明,氯化1-丁基-3-甲基咪唑盐离子液体对柴油中的中性含氮化合物具有高选择性脱除作用。

绿河油页岩中的开链醇化合物

研究了美国绿河盆地的 2 3个未成熟的露头油页岩样品 ,其中 13个样品取自Laney组 ,为半温湿半干燥气候下沉积于较浅的封闭水体的盐湖中心 ,含有丰富的有机质 ;另外 10个样品取自LumanTongue组 ,为潮湿气候下沉积于近岸的水体开放的淡水环境 ,其有机质含量较低。所有样品均富含从C11至C2 0 的同分异构体丰富的饱和类异戊二烯醇类化合物。此外还检出了一整套直链一元仲醇同系物 ,其碳数从 10至 33,而羟基可在任何理论上可能的碳位上。伯醇含量较低。研究结果表明 ,绿河油页岩中的有机质分别在沉积过程中和被抬升之后遭受了两次微生物降解。除伯醇的分布有生物来源特征外 ,其余的开链醇化合物是在绿河层系抬升至地表后微生物对其中烃类化合物降解的产物。文中将绿河油页岩有机质中异常高的氧指数归因于微生物降解 ,并探讨了其开链醇化合物的分布与物源、沉积环境及微生物降解程度的相关性。盐湖相Laney组的直链醇以低碳数组分为主 ,反映其有机质以菌藻为主的物源 ,与干燥的古气候相一致 ;淡水相LumanTongue组则以高碳数组分为主 ,有着明显优势的高等植物来源 ,与其潮湿的古气候相吻合。在沉积过程中 ,淡水相的LumanTongue组中的有机质遭受了比盐湖相的Laney组中的有机质更强的微生物降解 。

丹酰-L-苯丙氨酸和L-苯丙氨酸对小牛肠碱性磷酸酶抑制作用动力学的比较性研究

利用紫外分光光度法揭示了丹酰-L-苯丙氨酸对小牛肠碱性磷酸酶的选择性抑制作用,并比较性地研究了丹酰-L-苯丙氨酸和L-苯丙氨酸对小牛肠碱性磷酸酶的动力学抑制过程。结果表明在37℃和碱性磷酸酶工作的最佳pH值(pH10.4)的条件下,丹酰-L-苯丙氨酸与L-苯丙氨酸类似,能够有效抑制小牛肠碱性磷酸酶的活性;利用双倒数曲线拟合,判定丹酰-L-苯丙氨酸与L-苯丙氨酸的抑制类型均为反竞争性抑制,两者的抑制常数Ki均为mmol级。对丹酰-L-苯丙氨酸抑制小牛肠碱性磷酸酶的作用研究,不仅有助于进一步阐明L-苯丙氨酸对组织特异性碱性磷酸酶的选择性抑制机理,而且丹酰基团的存在也为荧光标定碱性磷酸酶的特效抑制剂提供了可能。

Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts

Bone is a dynamic tissue that is constantly renewed by the coordinated action of two cell types, i.e., the bone-resorbing osteoclasts and the bone-forming osteoblasts. However, in some circumstances, bone regeneration exceeds bone self repair capacities. This is notably often the case after bone fractures, osteolytic bone tumor surgery, or osteonecrosis. In this regard,bone tissue engineering with autologous or allogenic mesenchymal stem cells(MSCs) is been widely developed. MSCs can be isolated from bone marrow or other tissues such as adipose tissue or umbilical cord, and can be implanted in bone defects with or without prior amplification and stimulation. However, the outcome of most pre-clinical studies remains relatively disappointing. A better understanding of the successive steps and molecular mechanisms involved in MSC-osteoblastic differentiation appears to be crucial to optimize MSC-bone therapy. In this review, we first present the important growth factors that stimulate osteoblastogenesis. Then we review the main transcription factors that modulate osteoblast differentiation, and the microRNAs(miRs)that inhibit their expression. Finally, we also discuss articles dealing with the use of these factors and miRs in the development of new bone MSC therapy strategies. We particularly focus on the studies using human MSCs, since significant differences exist between osteoblast differentiation mechanisms in humans and mice for instance.

Effect of a single dose of malathion on spermatogenesisin mice

<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acetylcholinesterase (ACE) activity, spermatozoa (epididymal cauda counts and teratozoospermia), testis and plasma testosterone concentration) were evaluated at day 1,8, 16, 35 and 40 after treatment. Results: The sperm count was decreased significantly 24 h after treatment and teratozoospermia was increased at day 35 and 40. The height of the seminiferous epithelium and the diameter of tubular lumen were decreased at day 8. The percentage of tubular blockade was increased between day 8 and 35. A decrease in testosterone plasma level was observed at day 16 after treatment. Conclusion: Malathion damages male reproduction. The depletion of seminiferous tubules and the increase in teratozoospermia may be a genotoxic damage to the renewing spermatogonia, but the possibility of spermatogenic/ spermiogenic disfunction due to a decrease in the plasma testosterone level can not be ruled out.

Pesticide soil contamination mainly affects earthworm male reproductive parameters

Aim: To explore the effect of exposure to commercial Parathion~ (Pc) on the reproductive parameters (sperm and cocoon production and genotoxicity on male germ cells), the survival, the body weight and the gross anatomical changes in Eiseniafoetida. Methods: Three doses of Pc(1478, 739 and 444 mg/kg of soil) and three time intervals of exposure (5, 15 and 30 days) were used. Results: All treated animals were affected. An acute genotoxic effect, revealed by DNA fragmentation (comet assay), was seen by 5 days. Alterations in reproductive parameters were conspicuous in regard to the number of sperm, cocoons and worms born, and the histological observation of the gonads and seminal receptacles. In addition, the body weight and survival rate were decreased. Neuromuscular function was also affected. Conclusion: Earthworms are suitable bioindicators of chemical contamination of the soil, their advantage being their easy and economical handling

iCAP TQ ICP-MS准确测定环境样品中的砷和硒

本文介绍了Thermo Scientific TM iCAPTM TQ ICP-MS定量检测含稀土元素样品中砷和硒的方法,评估三重四极杆(TQ)-ICP-MS测量模式的性能,并与单四极杆(SQ)ICP-MS测量模式进行比较.为了验证方法的稳定性和准确性,在最佳参数条件下分析了深海沉积物和地球化学参考标准这两个样品.

Effect of malathion on the male reproductive organs of earthworms, Eisenia foetida

Aim: To observe the cytotoxic effect of the organophosphate insecticide malathion in the reproductive tissues of the earthworms, Eisenia foetida. Methods: Worms were nourished in soil treated with malathion at single sub-lethal doses of 0, 80, 150, 300 and 600 mg-kg^(-1) soil. (LD_(50) = 880 mg kg^(-1) soil) and evaluated on days 1, 5, 15 and 30 after exposure. The body weights were recorded and male reproductive organs evaluated. Results: Malathion-treated animals showed a significant reduction in body weight in a dose-dependent manner. Malathion treatment modified the disposition of spermatozoa in the basal epithelium of the spermatheca. The Br-deoxyuridine test showed a significant rise in cells in phase S on days 5 and 15. Also, a higher percentage of spermatogonia with fragmented DNA were observed by means of the TdT-mediated dUTP nick-end labeling (TUNEL) technique in the spermatheca of treated animals. Conclusion: Treatment with malathion decreased the body weight and the spermatic viability in spermatheca, altering the cell proliferation and modifying the DNA structure of spermatogonia.

Oxidative stress in tumor microenvironment--Its role in angiogenesis

The tumor angiogenesis process is believed to be dependent on an "angiogenic switch" formed by a cascade of biologic events as a consequence of the "cross-talk" between tumor cells and several components of local microenvironment including endothelial cells, macrophages, mast cells and stromal components. Oxidative stress represents an important stimulus that widely contributes to this angiogenic switch, which is particularly relevant in lungs, where oxidative stress is originated from different sources including the incomplete reduction of oxygen during respiration, exposure to hypoxia/reoxygenation, stimulated resident or chemoattracted immune cells to lung tissues, as well as by a variety of chemicals compounds. In the present review we highlight the role of oxidative stress in tumor angiogenesis as a key signal linked to other relevant actors in this complex process.

Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis

The sequence of events associated with the development of gastric cancer has been described as "the gastric precancerous cascade". This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori(H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the mostrelevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and mi RNAs in this context.

Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk： an exploratory genotype-environment interaction study

Aim： To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking. Methods： In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk. Results： The joint risk for smokers carrying Pro^＊ and MI^＊, Pro^＊ and GSTM1null or GSTM1 null and CYP1A1 MI^＊ variants was significantly higher （odds ratio [OR]： 13.13, 95% confidence interval [CI]： 2.41-71.36; OR： 3.97, 95% CI： 1.13-13.95 and OR： 6.87, 95% CI： 1.68-27.97, respectively） compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group （OR： 8.87, 95% CI： 1.25-62.71）. Conclusion： Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease

For 50 years ago was introduced L-3,4-dihydroxyphenylalanine（L-dopa） in Parkinson＇s disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson＇s disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson＇s disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson＇s disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson＇s disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.

Astrocytes protect dopaminergic neurons against aminochrome neurotoxicity

Astrocytes protect neurons by modulating neuronal function and survival.Astrocytes support neurons in several ways.They provide energy through the astrocyte-neuron lactate shuttle,protect neurons from excitotoxicity,and internalize neuronal lipid droplets to degrade fatty acids for neuronal metabolic and synaptic support,as well as by their high capacity for glutamate uptake and the conversion of glutamate to glutamine.A recent reported astrocyte system for protection of dopamine neurons against the neurotoxic products of dopamine,such as aminochrome and other o-quinones,were generated under neuromelanin synthesis by oxidizing dopamine catechol structure.Astrocytes secrete glutathione transferase M2-2 through exosomes that transport this enzyme into dopaminergic neurons to protect these neurons against aminochrome neurotoxicity.The role of this new astrocyte protective mechanism in Parkinson´s disease is discussed.

Sperm quality in mice acutely treated with parathion

Aim: To investigate the toxic effect of a single injection of the organophosphorous agropesticide, parathion, on sper-matogenesis in immature male mice. Methods: Seven-day old mice received a single injection of parathion intraperi-toneally at a dose of 1/3 LD_50. The epididymal sperm count, sperm morphology and chromatin thermal stability wereanalyzed 28 and 50 days after injection. Results: Sperm counts were decreased and teratozoospermia and thermal de-naturation of DNA increased after parathion injection. Sperm parameters were changed to a greater extent in younger an-imals, denoting a higher lability of spermatogenic process at its beginning. The damages could recover a long time afterparathion administration. Conclusion: Organophosphorous agropesticides are testicular toxicants, eliciting reversiblecytotoxic and cytogenetic alterations in germ cells.

A new mechanism for protection of dopaminergic neurons mediated by astrocytes

For a long time,the question about the mechanism involved in the degenerative process of the nigrostriatal system in Parkinson’s disease（PD）,resulting in the loss of dopaminergic neurons containing neuromelanin,has remained open.The discovery of genes associated with familial forms of PD,

Pan-cancer analyses demonstrate that ANKRD6 is associated with a poor prognosis and correlates with M2 macrophage infiltration in colon cancer

Objective:Ankyrin repeat domain-containing protein 6(ANKRD6)is an ankyrin repeat-containing protein which is structurally related to vertebrate inversin and Drosophila Diego.However,the correlations between ANKRD6 and tumor-infiltrating immune cells in cancers is not clear.Methods:ANKRD6 expression was analyzed by Oncomine,Tumor Immune Estimation Resource(TIMER)and Gene Expression Profiling Interactive Analysis(GEPIA).PrognoScan and GEPIA were used to evaluate the influence of ANKRD6 on clinical prognosis.TIMER and CIBERSORT were used to analyze correlations between ANKRD6 expression levels and tumor immune cell infiltrates.Immunohistochemical analysis of the relationship between ANKRD6 expression and overall survival,as well as the relationship between ANKRD6 expression and M2 macrophage infiltration,was performed.Results:High level of ANKRD6 expression was associated with poor prognosis of colon cancer.ANKRD6 expression level was positively correlated with infiltrating levels of CD8+T cells,CD4+T cells,macrophages,neutrophils and dendritic cells in colon cancer by using TIMER.Using CIBERSORT,we found that in plasma cells,CD8+T cells,CD4+memory resting T cells,follicular helper T cells and activated natural killer cells were significantly lower in the ANKRD6-high group than in the ANKRD6-low group.M0 and M2 macrophages were significantly higher in the ANKRD6-high group than in the ANKRD6-low group.Immunohistochemistry confirmed that M2 macrophage infiltration in the ANKRD6-high group significantly increased.Conclusions:The high ANKRD6 expression is associated with poor prognosis of colon cancer.ANKRD6 expression is positively correlated with M2 macrophage infiltration in colon cancer.