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NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

Oncology Research 2024年第2期32卷 283-296页

作者： XIANGDONG SUN HUIJUAN WEN FAZHAN LI ihtisham bukhari FEIFEI REN XIA XUE PENGYUAN ZHENG YANG MI Henan Key Laboratory for Helicobacter Pylori&Microbiota and GI Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Gastroenterology The Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and ***,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly *** constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor *** immune checkpoint genes were upregulated in the high-risk *** addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk ***,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk ***,the treatment of NMN showed increased proliferation of AGS and MKN45 *** addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN *** conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

关键词： NAD+ LncRNAs Cancer Cell infiltration Prognosis Tumor microenvironment

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Blood-testis barrier and spermatogenesis： lessons From genetically-modified mice

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Asian Journal of Andrology 2014年第4期16卷 572-580页

作者： Xiao-Hua Jiang ihtisham bukhari Wei Zheng Shi Yin Zheng Wang Howard J Cooke Qing-Hua Shi Hefei National Laboratory for Physical Sciences at Microscale School of Life Sciences University of Science and Technology of China Hefei China Medical Research Council Human Genetics Unit and Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh United Kingdom Institute of Physics Chinese Academy of Sciences Hefei China.

The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.

关键词： blood-testis barrier genetically-modified mouse seminiferous tubule sertoli cells spermatogenesis

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cGAS regulates the DNA damage response to maintain proliferative signaling in gastric cancer cells

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Oncology Research 2021年第2期29卷 87-103页

作者： BIN LIU HAIPENG LIU FEIFEI REN HANGFAN LIU ihtisham bukhari YUMING FU WANQINGWU MINGHAI ZHAO SHAOGONG ZHU HUI MO FAZHAN LI MICHAEL B.ZHENG YOUCAI TANG PENGYUAN ZHENG YANG MI Henan Key Laboratory of Helicobacter Pylori&Microbiota and Gastrointestinal Cancer The Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Academy of Medical Science Zhengzhou UniversityZhengzhouChina Clinical and Translational Research Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Gastrointestinal Surgery The Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Gastrointestinal Surgery Henan Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Gastrointestinal Surgery People Hospital of Zhengzhou UniversityZhengzhouChina Faculty of Science School of Interdisciplinary ScienceHonours Life SciencesMcMaster UniversityHamiltonONCanada

The activation of some oncogenes promote cancer cell proliferation and growth,facilitate cancer progression and metastasis by induce DNA replication stress,even genome *** of the cyclic GMP-AMP synthase(cGAS)mediates classical DNA sensing,is involved in genome instability,and is linked to various tumor development or ***,the function of cGAS in gastric cancer remains *** this study,the TCGA database and retrospective immunohistochemical analyses revealed substantially high cGAS expression in gastric cancer tissues and cell *** employing cGAS high-expression gastric cancer cell lines,including AGS and MKN45,ectopic silencing of cGAS caused a significant reduction in the proliferation of the cells,tumor growth,and mass in xenograft ***,database analysis predicted a possible involvement of cGAS in the DNA damage response(DDR),further data through cells revealed protein interactions of the cGAS and MRE11-RAD50-NBN(MRN)complex,which activated cell cycle checkpoints,even increased genome instability in gastric cancer cells,thereby contributing to gastric cancer progression and sensitivity to treatment with DNA damaging ***,the upregulation of cGAS significantly exacerbated the prognosis of gastric cancer patients while improving radiotherapeutic ***,we concluded that cGAS is involved in gastric cancer progression by fueling genome instability,implying that intervening in the cGAS pathway could be a practicable therapeutic approach for gastric cancer.

关键词： Gastric cancer Cell proliferation cGAS DNA damage response MRN complex

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A missense point mutation in COL10A1 identified with whole-genome deep sequencing in a 7-generation Pakistan dwarf family

A missense point mutation in COL10A1 identified with whole-g...

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2017中国长三角遗传学大会

作者： Chao Zhang Jiaojiao Liu Furhan Iqbal Yan Lu Saima Mustafa Firdous bukhari Haiyi Lou Ruiqing Fu Zhendong Wu Xiong Yang ihtisham bukhari Muhammad Aslam Shuhua Xu Chinese Academy of Sciences(CAS) Key Laboratory of Computational Biology Max Planck Independent Research Group on Population GenomicsCAS-MPG Partner Institute for Computational Biology(PICB)Shanghai Institutes for Biological SciencesCAS University of Chinese Academy of Sciences School of Life Science and Technology ShanghaiTech University Department of Zoology Institute of Pure and Applied BiologyBahauddin Zakariya University MultanPakistan Department of Biochemistry Biomarkers Research Program Prince Mutaib Chair for Biomarkers of OsteoporosisKing Saud University Collaborative Innovation Center of Genetics and Development

Disease-associated variants in the human genome are continually being identified using DNA sequencing technologies that are especially effective for Mendelian *** sequenced whole genome to high coverage(> 30 ×) of 6 members of a 7-generation family with dwarfism from a consanguineous tribe in Pakistan to locate the causal variant(s).We identified a missense variant rs111033552(c.2011 T>C[***671 Pro]) located in COLlOAl,encoding the alpha chain of type Ⅹ collagen,which is the most likely contributor to the dwarfism in this Pakistan *** further confirmed the variant in 22 family members using Sanger *** affected individuals are heterozygous for the missense mutation *** individual homozygous for this variant was *** suggests that the disorder is dominantly ***,the mutation was absent in 69,985 individuals representing>150 global *** advantage of whole-genome sequencing data,we also examined other variant forms such as copy number variation and insertion/deletion but failed to identify any other variants enriched in the affected ***,this variant had priority for linkage with *** 50 discovered variants in COLlOAl were annotated,12 variants(including rs111033552) of which are absent from global populations and highly conserved in evolution indicating the functional importance of COLlOAl despite its allelic heterogeneity.

关键词： Short stature COLlOAl Metaphyseal chondrodysplasia Schmid type Next generation sequencing Consanguinity

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TOL6BL突变导致减数分裂程序性DNA双链断裂无法产生和人类不孕

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Science Bulletin 2020年第24期65卷 2120-2129,M0006页

作者：焦玉莹樊岁兴 Nazish Jabeen 张欢 Ranjha Khan Ghulam Murtaza 蒋涵玮 Asim Ali 李阳鲍坚强张贝贝徐建泽许波 Hafiz Muhammad Jafar Hussain Qumar Zaman Ihsan Khan ihtisham bukhari Furhan Iqbal Ayesha Yousaf Sobia Dil Manan Khan Niaz Ahmad 马慧江小华张远伟史庆华 First Affiliated Hospital of University of Science and Technology of China Hefei National Laboratory for Physical Sciences at Microscalethe CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineCAS Center for Excellence in Molecular Cell ScienceCollaborative Innovation Center of Genetics and DevelopmentUniversity of Science and Technology of ChinaHefei 230027China Institute of Pure and Applied Biology Zoology DivisionBahauddin Zakariya UniversityMultan 60800Pakistan Shahbaz Sharif District Hospital Multan 60800Pakistan

我们找到一个近亲婚配后代不育家系,该家系有3位非梗阻性无精子症患者和1位原因不明的女性不孕患者.全外显子组测序结合Sanger测序分析发现TOP6BL的c.483dup T突变在该家系中与不孕呈隐性共分离.正常的TOP6BL可与SPO11β结合进而导致减... 详细信息

我们找到一个近亲婚配后代不育家系,该家系有3位非梗阻性无精子症患者和1位原因不明的女性不孕患者.全外显子组测序结合Sanger测序分析发现TOP6BL的c.483dup T突变在该家系中与不孕呈隐性共分离.正常的TOP6BL可与SPO11β结合进而导致减数分裂程序性DNA双链断裂(DSBs)产生,而该突变破坏了二者的结合.对家系中一位男患者的精母细胞进行分析,发现其同源染色体联会异常,减数分裂不能到达粗线期,且染色体轴上缺少减数分裂重组蛋白RPA和DMC1信号,表明其减数分裂程序性DSBs未能产生.我们制备了携带类似患者突变的小鼠,发现突变雄鼠具有与男患者相同的减数分裂异常,突变雌鼠不孕,其卵母细胞中程序性DSBs和减数分裂重组也不能发生,卵母细胞不能成熟.这些发现表明TOP6BL突变可导致人类不孕,为相关不孕不育患者的病因诊断和人工辅助生殖胚胎的遗传检查提供了分子标靶.

关键词：全外显子组测序非梗阻性无精子症病因诊断近亲婚配染色体联会 DNA双链断裂减数分裂异常精母细胞

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Evaluating the Impact of Different Tillage Regimes and Nitrogen Levels on Yield and Yield Components of Maize (Zea mays L.)

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American Journal of Plant Sciences 2016年第6期7卷 789-797页

作者： Muhammad Naeem Shahid M. Shahid Ibni Zamir ihtisham-Ul Haq M. Kamran Khan Mazhar Hussain Usman Afzal M. Asim ihtisham Ali Department of Agronomy University of Agriculture Faisalabad Pakistan

A field study to evaluate the impact of different tillage regimes and nitrogen levels on yield and yield components of maize (Zea mays L.), was conducted during autumn 2014 at Students Farm, Department of Agronomy, University of Agriculture, Faisalabad. The experiment was laid out in RCBD (Randomized Complete Block Design), with split plot arrangement having three replications. The experiment was comprised of three tillage regimes (Minimum, Conventional and Deep) and three nitrogen levels viz: 100, 200 and 300 kg•ha-1. Urea was used as a source of nitrogen, sulphate of potash as a source of potassium and triple super phosphate as a source of phosphorous. The amount of phosphorous and potash was constant in all the treatments i.e. 125 kg•ha-1 and 100 kg•ha-1 respectively. Results of present study are summarized as yield parameters are significantly affected by different nitrogen levels and tillage regimes. Maximum number of plants at harvest (7.93), number of grain rows per cob (17.70), number of grains per row (34.31), number of grains per cob (678.58), and cob weight (187.50 g) were observed in deep tillage at 200 kg•ha-1 nitrogen application. 1000-grain weight (275.52 g), biological yield (15.66 t•ha-1), grain yield (6.16 t•ha-1) and dried stalk yield (9.91 t•ha-1) were observed maximum in deep tillage at 200 kg•ha-1 nitrogen application. Harvest index significantly affected by tillage regimes and maximum harvest index (39.58%) were recorded in deep tillage which was statistically at par with conventional tillage (38.83%). It was concluded that higher grain yield of maize can be obtained by deep tillage with the application of 200 kg•ha-1 nitrogen application under the prevailing conditions of Faisalabad.

关键词： Tillage Regimes Nitrogen Levels Deep Tillage Biological Yield Harvest Index

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用GPS信噪比反演土壤含水量研究

用GPS信噪比反演土壤含水量研究

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作者：哈克（ihtisham Ul Haq）长安大学

学位级别：硕士

土壤含水量在自然环境中有着十分重要的作用,通过对其监测可以了解测区的水文波动情况,并且土壤含水量的变化是影响生态系统对气候变化的响应的关键因素之一。对土壤含水量进行稳定且精确的测量可为该地区的水文、气候、农业和灾害防治... 详细信息

土壤含水量在自然环境中有着十分重要的作用,通过对其监测可以了解测区的水文波动情况,并且土壤含水量的变化是影响生态系统对气候变化的响应的关键因素之一。对土壤含水量进行稳定且精确的测量可为该地区的水文、气候、农业和灾害防治提供重要的监测依据。常用的土壤含水量监测方法有现场采样法和电磁探针法,现场采样法虽然测量准确,但是费时费力,并且会对环境产生破坏;电磁探针由于设备的复杂性而难以适用于所有的土壤环境,并且这两种方法都只能在小范围区域内测量土壤含水量。遥感卫星虽然能获取大范围区域的土壤含水量,但是它的时间分辨率较低,并且没有地面监测数据对其测量的正确性进行验证。本文研究了基于地基GPS信噪比观测数据来反演土壤含水量的方法以及影响信噪比数据的因素,该方法可用于监测距离测站25米半径范围内的土壤含水量,对于降低数据获取的成本,减少不必要的人力,并提供长期稳定的土壤含水量监测数据有着重要的意义。本文的主要研究内容及成果具体如下:（1）介绍了利用GPS信噪比反演土壤含水量的原理。总结了多路径和信噪比的特点,并讨论了两者之间的关系,低高度角的信噪比数据受多径效应的影响较大。通过低阶多项式拟合移除直射信号而保留反射信号,并进行单位的转化,再通过L-S频谱分析和非线性最小二乘拟合计算得到相位参数,进而建立模型反演得到土壤含水量。（2）研究了相位和反射高度对土壤含水量的影响,并以两个GPS测站（p041和p038）为例,对相位和土壤含水量以及反射高度与土壤含水量的相关系数进行了比较。结果表明:相位和土壤含水量之间的相关性优于反射高度和土壤含水量之间的相关性;对于p041测站和p038测站,相位和土壤含水量之间的相关系数分别为0.808和0.702,反射高度与土壤含水量之间的相关系数分别为0.606和0.689;由于p038测站所处的位置地势平坦,植被覆盖较少,使得该测站的反射高度与土壤含水量之间的相关性比p041测站的好。（3）研究了降水、植被以及积雪等多种因素对信噪比数据的影响。由于降水引起的土壤含水量变化将导致信噪比数据的相位发生变化,并且信噪比的振幅会随土壤含水量的增加而增加;信号从植被冠层反射回去时会损失能量,从而导致信噪比的振幅降低,为了研究植被效应对信噪比的影响,采用了植被覆盖和裸露地表两种数据类型进行分析,结果表明:植被土壤振幅峰值为2.8 v/v,裸露土壤振幅峰值为2 v/v;下雪会导致反射信号的频率发生变化,可用该方法对雪深进行反演,本文使用两个不同的雪深数据,当雪深为0.53m时,反射信号强度为2.5 v/v,当雪深为0.15m时,反射信号强度接近0.15 v/v。

关键词： GNSS-IR 土壤含水量多路径信噪比干涉

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Fish as Bioindicator: Ecological Risk Assessment of Insecticide to Aquatic Organism Particularly Ctenopharyngodon idella

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Journal of Geoscience and Environment Protection 2021年第2期9卷 42-54页

作者： Naqash Khan Aamir Sultan Amir Ali Sahibzada Muhammad Haseeb Jan Waqar Khan ihtisham Ur Rahman Hazrat Usman Suleman Zahid Khan Ahsan Khan Department of Zoology University of Swabi Anbar Swabi Khyber Pakhtunkhwa Pakistan Department of Zoology University of Peshawar Khyber Pakhtunkhwa Pakistan

Repeatedly deposition of anthropogenic chemicals such as chlorpyrifos led to the risk of its associated unwanted toxicity to the non-targeted organisms. The present project was designed to assess the toxicity of chlorpyrifos, an organophosphorus insecticide, at different dose level and duration of exposure to elucidate its cellular and nuclear anomalies in erythrocytes and histopathological effect on brain and liver tissues of the fresh water fish (Ctenopharyngodon idella). The chlorpyrifos was used at 0.01 and 0.015 μL/L for a duration of 3, 6, 9, 12, and 15 days respectively. Alteration in functional markers such as cellular anomalies associated with exposed dosage was reported as swollen cells, swollen or enlarged cells, and hemolyzed cells followed by nuclear abnormalities stated as micronucleus, deformed nucleus and nuclear shift. The result indicated alterations observed in brain and liver tissues were categorized as necrosis, vacuolization, degeneration of neurons and hepatic necrosis, hepatolysis and hepatic vacuolization that were further scored on the basis of severity from 0 (normal) to 3 (severe). These effects significantly increased with the increase in dose level of chlorpyrifos and duration of exposure (p < 0.05). The present findings contributed that extended exposure of such chemicals to the aquatic ecosystems led to behavioral and histopathological alterations that may result in loss of normal functioning of the organs.

关键词： Histopathological Toxicological Cellular Abnormalities Nuclear Abnormalities Organophosphorus Chlorpyrifos

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Environmental Risk of Atrazine (Herbicide) to Brain, Gills and Liver Tissues of Fish Ctenopharyngodon idella(Valenciennes, 1844)

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Journal of Geoscience and Environment Protection 2021年第2期9卷 1-16页

作者： Waqar Ahmad Aamir Sultan Sahibzada Muhammad Haseeb Jan Aamir Ali ihtisham Ur Rahman Hazrat Usman Ahmad Sher Naqash Khan Suleman Zahid Khan Ahsan Khan Department of Zoology University of Swabi Anbar Swabi Khyber Pakhtunkhwa Pakistan Department of Zoology University of Peshawar Khyber Pakhtunkhwa Pakistan

The current study investigates the toxic effects of acute dose of an endocrine disruptor atrazine on Grass carp (Ctenepharyngodon idella) using histopathological changes as biomarkers. Histopathology is promising field for research in aquatic toxicology, in this manner vital organs;brain, gills, and liver tissues were inspected histological after exposing to sublethal groupings of atrazine 0.025 and 0.03 μl/L for 3, 6, 9, 12 and 15 days individually with equal untreated control group. Against various doses, rapid movements, gulping of air and jumping of fish to scat from toxic medium were noticed. Various severe (+++) morphological modifications in tissue were documented in comparison with control group comprised of degenerated neurons, vacuolization, inflammatory cells infiltration and neural necrosis in brain tissue. The most well-known gills tissue alteration at all concentrations of atrazine was epithelial hyperplasia, desquamation, epithelial lifting and smaller aneurism while hepatic injuries were described by overcast expanding of hepatocytes esteemed as cloudy swelling of hepatocytes followed by karyolysis, karyohexis and dilation of sinusoids which shows that atrazine introduction upgraded the toxicosis impacts with the increase concentration, influenced the strength of the fish, inferable from histological inconsistencies.

关键词： Histopathological Toxicological Brain Gills Liver

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Yield and Quality of Forage Oat (Avena sativaL.) Cultivars as Affected by Seed Inoculation with Nitrogenous Strains

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American Journal of Plant Sciences 2015年第19期6卷 3251-3259页

作者： Muhammad Saleem M. Shahid Ibni Zamir ihtishamul Haq M. Zahid Irshad M. Kamran Khan M. Asim Qamaruz Zaman ihtisham Ali Aman Khan Saeedur Rehman Department of Agronomy University of Agriculture Faisalabad Pakistan

Nitrogen availability can be enhanced with the application of nitrogen fixing bacteria and it may be helpful in increasing forage yield and improving quality of oat. Therefore, a field trial to evaluate the effect of seed inoculation with nitrogen fixing bacteria on forage yield and quality of oat was carried out at Agronomic Research Area, University of Agriculture, Faisalabad during Rabi season 2013-14. The experiment was laid out in Randomized Complete Block Design (RCBD) with factorial arrangements using three replications. The experiment was comprised of two integrated approaches. The first approach was oat cultivars consisting of four treatments, V1 (AVON), V2 (S-2000), V3 (S-2011) and V4 (PD2LV65) and the second approach was seed inoculation consisting of three treatments, S0 (control), S1 (Azotobacter spp.), S2 (Azospirillum spp.). Fisher’s analysis of variance technique was used for statistically interpretation of data by using least significant difference (LSD) test at 5% level of probability. Nitrogen fixing bacteria significantly affect the germination count (m2), plant height (cm), number of tillers (m2), number of leaves per tiller, leaf area per tiller (cm2), green forage yield (t·ha-1) and dry matter yield (t ha-1). The maximum green forage yield (85.2 t·ha-1), dry matter yield (14.1 t ·ha-1) and crude protein (11.5%) were recorded where Azotobacter inoculation was applied. The interaction between cultivars and nitrogenous strains was significant for green forage yield (t·ha-1), dry matter yield (t·ha-1) and crude protein (%). Conclusion showed that cultivar Sargodha-2011 which was inoculated with Azotobacter spp. gave higher forage yield of good quality.

关键词： Oat Cultivars Nitrogenous Strains Quality and Forage Yield

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