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Neural Regeneration research 2023年第2期18卷 322-323页

作者： Hannah Musco Julie A.Wixey UQ centre for clinical research Faculty of MedicineUniversity of QueenslandQueenslandAustralia

Fetal growth restriction(FGR)is one of the most common contributors to increased risk of mortality in the fetal/neonatal period and long-term morbidity in the infant(Malhotra et al.,2019).FGR can arise from many pathophysiological processes associated with maternal,fetal,genetic,or placental compromise;however,placental insufficiency is the most common cause of FGR.Placental insufficiency during pregnancy results in chronic fetal hypoxia where a lack of oxygen and nutrients supply to the developing fetus impacts normal development of the fetus.

关键词： fetal fetus insufficiency

Hypoxia-ischemia in the immature rodent brain impairs serotonergic neuronal function in certain dorsal raphé nuclei

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Neural Regeneration research 2020年第3期15卷 457-463页

作者： Hanna E.Reinebrant Julie A.Wixey Kathryn M.Buller UQ centre for clinical research Faculty of Medicine The University of Queensland

Neonatal hypoxia-ischemia(HI)results in losses of serotonergic neurons in specific dorsal raphe nuclei.However,not all serotonergic raphe neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate.The main objective of this study was to determine how serotonergic neurons,remaining in the dorsal raphe nuclei after neonatal HI,respond to an external stimulus(restraint stress).On postnatal day 3(P3),male rat pups were randomly allocated to one of the following groups:(i)control+no restraint(n=5),(ii)control+restraint(n=6),(iii)P3 HI+no restraint(n=5)or(iv)P3 HI+restraint(n=7).In the two HI groups,rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6%O2 for 30 minutes.Six weeks after P3 HI,on P45,rats were subjected to restraint stress for 30 minutes.Using dual immunolabeling for Fos protein,a marker for neuronal activity,and serotonin(5-hydroxytrypamine;5-HT),numbers of Fos-positive 5-HT neurons were determined in five dorsal raphe nuclei.We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphe nuclei compared to control animals.However,following P3 HI,the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphe ventrolateral,interfascicular and ventral nuclei compared with control animals exposed to restraint stress.In contrast,numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphe dorsal and caudal nuclei were not affected by P3 HI.These data indicate that not only are dorsal raphe serotonergic neurons lost after neonatal HI,but also remaining dorsal raphe serotonergic neurons have reduced differential functional viability in response to an external stimulus.Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC)on February 27,2009.

关键词： dorsal raphe nuclei Fos hypoxia-ischemia neonate newborn brain injury preterm restraint stress serotonin

Could serotonin play a role in abnormal brain outcomes in fetal growth restriction?

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Neural Regeneration research 2023年第3期18卷 543-544页

作者： Kate Beecher Julie A.Wixey UQ centre for clinical research Faculty of MedicineThe University of QueenslandHerstonQLDAustralia

Fetal growth restriction(FGR)describes a fetus that has not grown to its expected biological potential in utero.FGR can result from maternal,fetal,or placental complications,though it is commonly caused by placental insufficiency.The prolonged hypoxic environment the FGR fetus is exposed to has detrimental effects on the newborn,which extends to adverse long-term neurological outcomes in a significant proportion of FGR infants(Malhotra et al.,2019).Unfortunately,there are currently no therapies to reduce the adverse neurological outcomes in FGR.Neuronal injury is evident in the FGR brain,and therefore understanding which neurons are lost and how they are lost will aid in the selection of treatment options for FGR.

关键词： fetal fetus insufficiency

The N-formyl peptide receptors: contemporary roles in neuronal function and dysfunction

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Neural Regeneration research 2020年第7期15卷 1191-1198页

作者： Peter J.G. Cussell Margarita Gomez Escalada Nathaniel G.N. Milton Andrew W.J. Paterson centre for Biomedical Science research School of Clinical and Applied Sciences Leeds Beckett University

N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within neuronal tissues and markedly in the central nervous system,where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease,as well as neurological cancers such as neuroblastoma.Whilst the homeostatic function of FPRs in the nervous system is currently undefined,a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which,upon greater characterisation,could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury,stroke and neurodegeneration.This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting,and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system,and for their potential to open the door to novel neuronal regeneration therapies.

关键词： Alzheimer's disease formyl peptide receptor neural regeneration neuroblastoma neurodegeneration neuroinflammation neuronal differentiation stroke

Improving brain outcomes in the growth restricted newborn: treating after birth

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Neural Regeneration research 2021年第5期16卷 978-979页

作者： Julie A.Wixey Stella Tracey Bjorkman UQ centre for clinical research Faculty of MedicineThe University of QueenslandHerstonQueenslandAustralia

Intrauterine growth restriction(IUGR)occurs when a baby is unable to grow normally due to receiving inadequate nutrients while developing in the womb.IUGR is a leading cause of perinatal death and longterm disability.The fetal brain is particularly vulnerable to IUGR conditions and adverse outcomes range from learning,attention and behavioral difficulties,to cerebral palsy.Due to medical advancements,more IUGR babies now survive,resulting in an even greater burden of disability.

关键词： restricted IUGR advancement

Evaluation of DNA damage profile in obese women and its association to risk of metabolic syndrome,polycystic ovary syndrome and recurrent preeclampsia

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Genes & Diseases 2018年第4期5卷 367-373页

作者： Moushira Zaki Walaa Basha Hala T.El-Bassyouni Safinaz El-Toukhy Tamer Hussein Biological Anthropology Department Medical Research DivisionNational Research CentreCairoEgypt clinical Genetics Department National Research CentreCairoEgypt Medical Biochemistry Department Medical Research DivisionNational Research CentreCairoEgypt Reproductive Health research Department Medical Research DivisionNational Research CentreCairoEgypt

Metabolic syndrome(MS)is a cluster of metabolic abnormalities.Obesity and MS are always accompanied by elevated oxidative stress which might affect cellular biomolecules such as DNA.The aim of the present study is to investigate DNA damage profile in obese premenopausal women and its relation to the risk of MS,polycystic ovary syndrome(PCOS)and history of recurrent pre-eclampsia.The study included 90 obese women included cases with MS(nZ30),PCOS(n Z30)and previous history of recurrent preeclampsia(nZ30)and,age-matched healthy non-obese control women(n Z 50).The assessment of leukocyte DNA damage was done by comet assay for all cases and controls.Anthropometry and biochemical parameters have been measured.Results showed that mean percent of DNA damage was significantly higher in MS,PCOS as well as in women with the recurrent preeclampsia as compared to healthy controls.The high level of mean DNA damage frequency in obese women was significantly associated with the increased number of metabolic syndrome components.Cases with 2,3 and 3e5 components showed significantly higher levels of DNA damage than controls.Moreover,cases with 3e5 MS components showed significant higher DNA compared to those with the two components.Regarding PCOS,significant positive association between the mean frequency of DNA damage and waist circumference was observed.The study suggests that metabolic abnormalities,PCOS and recurrent pre-eclampsia might be contributed in development of DNA damage in obese women.DNA damage can serve as an early marker for obesity complications in premenopausal women.

关键词： DNA damage Metabolic components Obesity PCOS Recurrent preeclampsia

Targeting inflammation to reduce brain injury in growth restricted newborns:a potential treatment?

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Neural Regeneration research 2017年第11期12卷 1804-1806页

作者： Julie A Wixey Paul B Colditz Stella Tracey Bjorkman centre for clinical research Faculty of MedicineThe University of QueenslandHerstonQueenslandAustralia

Introduction： Intrauterine growth restriction （IUGR） is commonly caused by placental insufficiency, resulting in a chronic hypoxic environment and subsequent abnormal fetal development. The developing brain is particularly vulnerable to IUGR conditions. Multiple causal factors associated with brain injury in fetal growth restriction include the timing of placental insufficiency, onset and subsequent severity of fetal compromise, fetal cerebrovascular response and the redistribution of brain blood flow. Although a significant proportion of IUGR infants exhibit adverse long-term neu- rological outcomes, relatively few studies have focused on the mechanisms of brain injury in the IUGR neonate. Clini- cal imaging studies of IUGR infants demonstrate alterations in grey matter and white matter volume and structure （Tolsa et al., 2004; Esteban et al., 2010; Padilla et al., 2015）. Cortical grey matter volume is reduced by up to 28% compared with control infants （Tolsa et al., 2004） and both white and grey matter show structural changes （Esteban et al., 2010）. These structural changes persist at 1 year of age and are associated with significant developmental disabilities （Tolsa et al., 2004;

关键词： Targeting inflammation brain injury

Neonatal seizures and disruption to neurotransmitter systems

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Neural Regeneration research 2017年第2期12卷 216-217页

作者： Stephanie M.Miller Kate Goasdoue S.Tracey Bjorkman The University of Queensland UQ Centre for Clinical ResearchHerston QLD Australia

Seizure disorders and epilepsies are well documented to be associated with long-term neurological and cognitive deficits in the adult and pediatric patients,but what about seizures in the newborn？The neonatal brain i... 详细信息

关键词： AEDs Neonatal seizures and disruption to neurotransmitter systems GABAA Cl NMDA

Association of vitamin D receptor gene polymorphism(VDR)with vitamin D deficiency,metabolic and inflammatory markers in Egyptian obese women

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Genes & Diseases 2017年第3期4卷 176-182页

作者： Moushira Zaki Sanaa Kamal Walaa ABasha Eman Youness Wafaa Ezzat Hala El-Bassyouni Khalda Amr Biological Anthropology Department National Research CentreGizaEgypt Medical Biochemistry Department National Research CentreGizaEgypt Internal Medicine Department National Research CentreGizaEgypt clinical Genetics Department National Research CentreCairoEgypt Medical Molecular Genetics Department National Research CentreEgypt

Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,serum 25-hydroxy vitamin D,metabolic and inflammatory biomarkers in Egyptian obese women.The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels.Their age ranged between 25 and 35 years.Inflammatory biomarkers(interleukin-6 and C-reactive protein)and serum 25(OH)D were measured by enzyme-linked immunosorbent assay.Insulin resistance(IR)was determined by the homeostasis model assessment of insulin resistance(HOMA-IR).Vitamin D receptor(VDR)gene polymorphisms of FokI,ApaI,and TaqI were studied by PCR using the restriction fragment length polymorphism(RFLP)technique.Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls.Multivariable-logistic regression showed associations between 25(OH)D deficiency and metabolic components when comparing cases with controls.Moreover,cases carrying polymorphic alleles showed significant lower levels of serum 25(OH)D and higher HOMA-IR,blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency.Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers.Moreover,VDR polymorphisms play important role in immune and inflammation status.

关键词： Inflammatory biomarkers Obese women Vitamin D deficiency Vitamin D receptor(VDR)gene polymorphism Egyptian

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis

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Chinese Medical Journal 2021年第18期134卷 2196-2204页

作者： Liang Yu Tian-Lei Xu Lin Zhang Shuo-Hao Shen Yue-Lu Zhu Hui Fang Hai-Zeng Zhang Department of Colorectal Surgery National Cancer Centre/National Clinical Research Centre for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Lab of Molecular Oncology National Cancer Centre/National Clinical Research Centre for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pathology National Cancer Centre/National Clinical Research Centre for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiation Oncology National Cancer Centre/National Clinical Research Centre for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy(NCRT).This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis.Methods:In total,1296 patients with NCRT or post-operative chemoradiotherapy(PCRT)were enrolled in this study between January 2008 and December 2015.Propensity score matching was used to correct for differences in baseline characteristics between the two groups.After propensity score matching,the metastasis pattern,including metastasis sites and timing,was compared and analyzed.Results:After propensity score matching,there were 408 patients in the PCRT group and 245 patients in the NCRT group.NCRT significantly reduced local recurrence(4.1%vs.10.3%,P=0.004),but not distant metastases(28.2%vs.27.9%,P=0.924)compared with PCRT.In both the NCRT and PCRT groups,the most common metastasis site was the lung,followed by the liver.The NCRT group developed local recurrence and distant metastases later than the PCRT group(median time:29.2[18.8,52.0]months vs.18.7[13.3,30.0]months,Z=–2.342,P=0.019;and 21.2[12.2,33.8]vs.16.4[9.3,27.9]months,Z=–1.765,P=0.035,respectively).The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group(39/114,34.2%)and NCRT group(21/69,30.4%).However,20.3%(14/69)of the distant metastases appeared in the 3rd year in the NCRT group,while this number was only 13.2%(15/114)in the PCRT group.Conclusions:The predominant site of distant metastases was the lung,followed by the liver,for both the NCRT group and PCRT group.NCRT did not influence the predominant site of distant metastases,but the NCRT group developed local recurrence and distant metastases later than the PCRT group.The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.

关键词： Locally advanced rectal cancer Metastases pattern Neoadjuvant chemoradiotherapy Propensity score matching