Yongjian Zhu

Targeting DNA repair pathways: a novel approach to reduce cancer therapeutic resistance.

Increased chemo-resistance and radio-resistance of cancer cells is a major obstacle in the treatment and management of malignant cancers. An important mechanism that underlies the development of such therapeutic resistance is that cancer cells recognize DNA lesions induced by DNA-damaging agents and by ionizing radiation, and repair these lesions by activating various DNA repair pathways. Therefore, Use of pharmacological agents that can inhibit certain DNA repair pathways in cancer cells has the potential for enhancing the targeted cytotoxicity of anticancer treatments and reversing the associated therapeutic resistance associated with DNA repair; such agents, offering a promising opportunity to achieve better therapeutic efficacy. Here we review the major DNA repair pathways and discuss recent advances in the development of novel inhibitors of DNA repair pathways; many of these agents are under preclinical/clinical investigation.

THE EFFECT OF MICROWAVE EMMISION FROM MOBILE PHONES ON NEURON SURVIVAL IN RAT CENTRAL NERVOUS SYSTEM

To investigate the effect of microwave emitted by mobile phones on the rat central nervous system (CNS), in vitro cultured cortical neuronal cells and in vivo rat’s brain were exposed to the electromagnetic waves emitted by a microwave transmitter that mimics the working frequency of mobile phones. Trypan blue staining and terminal deoxynucleotidy transferase-mediated dUTP nick-end labeling (TUNEL) were used to determine the survival state of neuronal cells while immunohistochemistry method was used to determine the expression level of Bcl-2 and Bax. Our results show that microwave lead to significant cell death in culture and more in vivo brain neuronal cells were stained positive for TUNEL, Bax and Bcl-2 in rats with cranial defect after exposure than that for † To whom correspondence should be addressed: Department of Neurosurgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, People’s Republic of China

Minimally invasive removal of lumbar intradural extramedullary lesions using the interlaminar approach.

OBJECT Posterior midline laminectomy or hemilaminectomy has been successfully applied as the standard microsurgical technique for the treatment of spinal intradural pathologies. However, the associated risks of postoperative spinal instability increase the need for subsequent fusion surgery to prevent potential long-term spinal deformity. Continuous efforts have been made to minimize injuries to the surrounding tissue resulting from surgical manipulations. The authors report here their experiences with a novel minimally invasive surgical approach, namely the interlaminar approach, for the treatment of lumbar intraspinal tumors. METHODS A retrospective review was conducted of patients at the Second Affiliated Hospital of Zhejiang University School of Medicine who underwent minimally invasive resection of lumbar intradural-extramedullary tumors. By using an operative microscope, in addition to an endoscope when necessary, the authors were able to treat all patients with a unilateral, paramedian, bone-sparing interlaminar technique. Data including preoperative neurological status, tumor location, size, pathological diagnosis, extension of resections, intraoperative blood loss, length of hospital stay, and clinical outcomes were obtained through clinical and radiological examinations. RESULTS Eighteen patients diagnosed with lumbar intradural-extramedullary tumors were treated from October 2013 to March 2015 by this interlaminar technique. A microscope was used in 15 cases, and the remaining 3 cases were treated using a microscope as well as an endoscope. There were 14 schwannomas, 2 ependymomas, 1 epidermoid cyst, and 1 enterogenous cyst. Postoperative radiological follow-up revealed complete removal of all the lesions and no signs of bone defects in the lamina. At clinical follow-up, 14 of the 18 patients had less pain, and patients motor/sensory functions improved or remained normal in all cases except 1. CONClUSIONS When meeting certain selection criteria, intradural-extramedullary lumbar tumors, especially schwannomas, can be completely and safely resected through a less-invasive interlaminar approach using a microscope, or a microscope in addition to an endoscope when necessary. This approach was advantageous because it caused even less bone destruction, resulting in better postoperative spinal stability, no need for facetectomy and fusion, and quicker functional recovery for the patients. Individualized surgical planning according to preoperative radiological findings is key to a successful microsurgical resection of these lesions through the interlaminar space.

Microscope-assisted endoscopic interlaminar ligation of spinal arteriovenous fistulas: technical note

Spinal dural arteriovenous fistulas (SDAVFs) are the most common type of spinal arteriovenous malformations, and microsurgical ligation is the treatment modality most frequently used for these lesions. Developments in endoscopic techniques have made endoscopy an even less invasive alternative to routine microsurgical approaches in spine surgery, but endoscopic management of SDAVF or other intradural spinal lesions has not been reported to date. The authors describe the use of a microscope-assisted endoscopic interlaminar approach for the ligation of the proximal draining vein of an L-1 SDAVF in a 58-year-old man. A complete cure was confirmed by postoperative angiography. The postoperative course was uneventful, and short-term follow-up showed improvements in the patients neurological function. The authors conclude that the endoscopic interlaminar approach with microscope assistance is a safe, minimally invasive, innovative technique for the surgical management of SDAVFs in selected patients.

The Presence of Hepatitis B Surface Antigen in the Ova of Pregnant Women and Its Relationship with Intra-Uterine Infection by Hepatitis B Virus

Vertical transmission of hepatitis B virus (HBV) has been proposed to play an important role in mother-to-child transmission, although the extent to which vertical transmission via oocytes contributes to neonatal HBV infection remains unknown. Ovarian biopsies were collected during caesarean sections in 68 clinically asymptomatic pregnant women who were carriers of HBV. The presence of hepatitis B surface antigen (HBsAg) in the ova of pregnant women was determined by immunohistochemistry. Serum markers of HBV infection in pregnant women and their neonates were analysed. It was found that, of 68 women, the ova were positive for HBsAg in only one woman and her neonate was negative for any serum HBV markers 3 days after birth. Of 68 neonates, one was positive for serum HBV markers 3 days after birth and his mothers ova were negative for HBsAg. These findings indicate that vertical transmission via oocytes may not be the major route of HBV intra-uterine infection.

Effects of electromagnetic fields exposure on plasma hormonal and inflammatory pathway biomarkers in male workers of a power plant

PurposeThe potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant.MethodsSeventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-κB, heat–shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay.ResultsEMF exposure group had statistically significantly lower levels of testosterone (βxa0=xa0−0.3xa0nmol/L, Pxa0=xa00.015), testosterone/estradiol (T/E2) ratio (βxa0=xa0−15.6, Pxa0=xa00.037), and NF-κB (βxa0=xa0−20.8xa0ng/L, Pxa0=xa00.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found.ConclusionsThe findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.

Spontaneous thoracic ventral spinal subdural hematoma mimicking a tumoral lesion: a case report

IntroductionSpinal subdural hematoma is rare and can cause serious neurological symptoms. Sometimes, idiopathic spinal subdural hematoma can spontaneously occur without any identifiable underlying etiologies. In this report, we present such an uncommon case of paraplegia caused by idiopathic spinal subdural hematoma that was successfully managed by laminectomy.Case presentationA 45-year-old Chinese woman presented with sudden onset of progressive asthenia and numbness in both lower extremities, accompanied by difficulty in micturition. An initial non-contrast spinal magnetic resonance imaging at a local hospital suggested a spinal subdural tumoral hematoma at the T9 level. She was referred to our hospital and an emergency laminectomy from T8 to T10 was performed 22 hours after onset of her initial symptoms. However, nothing but a hematoma was identified during the operation, and a final diagnosis of spontaneous acute spinal subdural hematoma was concluded. She had partial return of sensations and voluntary movement after the operation.ConclusionsOn imaging findings, spinal subdural hematoma could manifest as focal and independent from the dura matter, and, therefore, it should be included in the differential diagnosis of medullary compressive lesions.

Effects of electromagnetic fields from mobile phones on depression and anxiety after titanium mesh cranioplasty among patients with traumatic brain injury.

Abstract Objective: To explore the effects of radiofrequency-electromagnetic fields (RF-EMFs) from mobile phones on depression and anxiety after titanium mesh cranioplasty among patients with traumatic brain injury (TBI). Methods: Two hundred and twenty patients with TBI and titanium mesh cranioplasty who were hospitalized from 2008–2012 were recruited in this study. From November–December 2012, the relevant information was surveyed including socio-demographic characteristics, lifestyle variables, injury-related information, RF-EMF exposure of mobile phone, Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). Associations of RF-EMFs exposure after titanium mesh cranioplasty with SAS and SDS were respectively estimated by multivariable linear regression models. Results: The patients with long durations of mobile phone use (βu2009=u2009−6.6, pu2009=u20090.002), long individual call duration (β = −5.3, pu2009=u20090.012), more daily calls (βu2009=u2009−3.6, pu2009=u20090.027), invariably answer call immediately (βu2009=u2009−3.9, pu2009=u20090.022) and high comprehensive exposure level (βu2009=u2009−4.8, pu2009=u20090.003) had a lower score of depression compared with those without a mobile phone. Moreover, an ipsilateral and contralateral answering phone enhanced the protective effect on depression. Individuals with a long duration of mobile phone use had a lower score of anxiety (βu2009=u2009−4.2, pu2009=u20090.008), while those with a bilateral answering phone had higher anxiety (βu2009=u20093.9, pu2009=u20090.012) in comparison to those without a mobile phone. Conclusion: RF-EMFs after cranioplasty were significantly associated with the lower risk of depression and anxiety status among patients with TBI. Chronic and frequent RF-EMFs exposure may improve psychiatric disorders among patients with TBI.

The cytotoxic effect of β-elemene against malignant glioma is enhanced by base-excision repair inhibitor methoxyamine

This study investigated the effects of β-elemenexa0+xa0methoxyamine, a DNA base-excision repair inhibitor, on the inhibition of glioma growth. We treated C6 and SHG44 glioma cells with β-elemene and methoxyamine individually or in combinations, and subsequently analyzed cellular survivals by MTT assay. Comet assay, γ-H2AX focus formation assay and Western-blot were performed to investigate whether the observed cytotoxicity was associates with DNA damages. Finally, a xenograft tumor model was established in nude mice with C6 cells to analyze in vivo tumor inhibition effects of β-elemene, which was followed by determination of the expression of anti-apoptotic protein Bcl-2 via immunohistochemistry staining. Results showed that β-elemene could significantly inhibit the growth of glioma cells in a dose- and time-dependent manner. The combination of methoxyamine with β-elemene could result in a greater extent of DNA injuries in vitro. Furthermore, in vivo tumors exhibited a marked shrinkage in volume in β-elemenexa0+xa0methoxyamine treatment group. Immunohistochemistry analysis of the tumor tissues showed a distinctive decrease in Bcl-2 staining in β-elemene (56xa0%) and β-elemenexa0+xa0methoxyamine (36xa0%) groups when compared with the negative control (77xa0%). In conclusion, β-elemene exhibits a significant cytotoxic effect against glioma cells both in vitro and in vivo, which is likely to be mediated by its potential to damage tumor cell DNA and activate apoptotic pathway. Such growth inhibition effect of β-elemene could be potentiated by methoxyamine co-administration. Therefore, a combination of the two agents as a novel chemotherapeutic option for glioma merits further investigations.

Effects of Cilostazol on Thrombospondin-1 (TSP-1) Expression Changes in the Myocardium of Diabetic Rats

Myocardial protective effects of the phosphodiesterase 3 inhibitor, cilostazol, in streptozotocin-induced diabetic rats were investigated. Four weeks after induction of diabetes, we measured thrombospondin-1 (TSP-1) expression in the left ventricular myocardium. Microstructural and ultrastructural changes were also analysed. Four weeks after the induction of diabetes there were significant differences in body weight and blood glucose between the control, diabetic and cilostazol-treated diabetic animals. TSP-1 expression was significantly increased in the myocardium of diabetic rats compared with the control group. Although significantly higher than the control group, TSP-1 expression was significantly lower in the cilostazol group compared with the diabetes group. There were obvious ultrastructural changes in the myocardium of diabetic rats, which were rarely seen in cilostazol-treated diabetic rats. In conclusion, this study provides experimental evidence that cilostazol treatment of diabetic rats effectively prevents pathological myocardial alterations, possibly via the down-regulation of TSP-1 expression.