http://www.jbiomedsci.com The most accessed research articles published by Journal of Biomedical Science 2012-01-27T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves. http://www.jbiomedsci.com/content/16/1/108 Anuradha Subramanian Uma Maheswari Krishnan Swaminathan Sethuraman Journal of Biomedical Science 2009, null:108 2009-11-25T00:00:00Z doi:10.1186/1423-0127-16-108 /content/figures/1423-0127-16-108-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 108 2009-11-25T00:00:00Z XML Background: To explore the feasibility of constructing engineered myocardial tissues (EMTs) in vivo, using polylactic acid -co-glycolic acid (PLGA) for scaffold and cardiomyocyte-like cells derived from bone marrow mesenchymal stem cells (BMMSCs) for seeded cells. Methods: BMMSCs were isolated from femur and tibia of Sprague-Dawley (SD) rats by density-gradient centrifugation .The third passage cells were treated with 10mumol/L 5-azacytidine (5-aza) and 0.1mumol/L angiotensin II (Ang II) for 24h, followed by culturing in complete medium for 3 weeks to differentiated into cardiomyocyte-like cells. The cardiomyocyte-like cells were seeded into PLGA scaffolds to form the grafts .The grafts were cultured in the incubator for three days and then implanted into the peritoneal cavity of SD rats. Four weeks later, routine hematoxylin-eosin (HE) staining, immunohistochemical staining for myocardium-specific cardiac troponin I (cTnI), scanning electron microscopy and transmission electron microscopy were used to analyze the morphology and microconstruction of the EMTs in host rats. Results: HE staining showed that the cardiomyocyte-like cells distributed equally in the PLGA scaffold, and the nuclei arranged in the spindle shape. Immunohistochemical staining revealed that majority of engrafted cells in the PLGA -Cardiomyocyte-like cells group were positive for cTnI. Scanning electron microscopy showed that the inoculated cells well attached to PLGA and grew in 3 dimensions in construct. Transmission electron microscopy showed that the EMTs contained well arranged myofilaments paralleled to the longitudinal cell axis, the cells were rich in endoplasmic reticulum and mitochondria, while desmosomes, gap junction and Z line-like substances were also can be observed as well within the engrafted cells. Conclusion: We have developed an in vivo method to construct engineered myocardial tissue. The in vivo microenvironment helped engrafted cells/tissue survive and share similarities with the native heart tissue. http://www.jbiomedsci.com/content/19/1/6 Yujie Xing Anlin Lv Li Wang Xuebo Yan Wei Zhao Feng Cao Journal of Biomedical Science 2012, null:6 2012-01-12T00:00:00Z doi:10.1186/1423-0127-19-6 /content/figures/1423-0127-19-6-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 6 2012-01-12T00:00:00Z PDF Background: The covalently closed-circular DNA (cccDNA) of hepatitis B virus (HBV) is associated with viral persistence in HBV-infected hepatocytes. However, the regulation of cccDNA and its transcription in the host cells at different growth stages is not well understood. Methods: We took advantages of a stably HBV-producing cell line, 1.3ES2, and examine the dynamic changes of HBV cccDNA, viral transcripts, and viral replication intermediates in different cellular growth stages. Results: In this study, we showed that cccDNA increased suddenly in the initial proliferation phase of cell growth, probably attributable to its nuclear replenishment by intracellular nucleocapsids. The amount of cccDNA then decreased dramatically in the cells during their exponential proliferation similar to the loss of extrachromosomal plasmid DNA during cell division, after which it accumulated gradually while the host cells grew to confluency. We found that cccDNA was reduced in dividing cells and could be removed when proliferating cells were subjected to long term of lamivudine (3TC) treatment. The amounts of viral replicative intermediates were rapidly reduced in these proliferating cells and were significantly increased after cells reaching confluency. The expression levels of viral transcripts were increased in parallel with the elevated expression of hepatic transcription factors (HNF4α, CEBPα, PPARα, etc.) during cell growth confluency. The HBV transcripts were transcribed from both integrated viral genome and cccDNA, however the transcriptional abilities of cccDNA was less efficient then that from integrated viral genome in all cell growth stages. We also noted increases in the accumulation of intracellular viral particles and the secretion of mature virions as the cells reached confluency and ceased to grow. Conclusions: Based on the dynamics of HBV replication, we propose that HBV replication is modulated differently in the different stages of cell growth, and can be divided into three phases (initial proliferation phase, exponential proliferation phase and growth confluency phase) according to the cell growth curve. The regulation of cccDNA in different cell growth phase and its importance regarding HBV replication are discussed. http://www.jbiomedsci.com/content/18/1/96 Chin-Liew Chong Mong-Liang Chen Yi-Chieh Wu Kuen-Nan Tsai Chien-Chiao Huang Cheng-po Hu King-Song Jeng Yu-Chi Chou Chungming Chang Journal of Biomedical Science 2011, null:96 2011-12-30T00:00:00Z doi:10.1186/1423-0127-18-96 /content/figures/1423-0127-18-96-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 96 2011-12-30T00:00:00Z XML Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment. http://www.jbiomedsci.com/content/17/1/21 S Patyar R Joshi D Prasad Byrav A Prakash B Medhi B Das Journal of Biomedical Science 2010, null:21 2010-03-23T00:00:00Z doi:10.1186/1423-0127-17-21 /content/figures/1423-0127-17-21-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 21 2010-03-23T00:00:00Z XML Background: The effective therapies for oral cancer patients of stage III and IV are generally surgical excision and radiation combined with adjuvant chemotherapy using 5-Fu and Cisplatin. However, the five-year survival rate is still less than 30% in Taiwan. Therefore, evaluation of effective drugs for oral cancer treatment is an important issue. Many studies indicated that aurora kinases (A, B and C) were potential targets for cancer therapies. Reversine was proved to be a novel aurora kinases inhibitor with lower toxicity recently. In this study, the potentiality for reversine as an anticancer agent in oral squamous cell carcinoma (OSCC) was evaluated. Methods: Effects of reversine on cell growth, cell cycle progress, apoptosis, and autophagy were evaluated mainly by cell counting, flow cytometry, immunoblot, and immunofluorescence. Results: The results demonstrated that reversine significantly suppressed the proliferation of two OSCC cell lines (OC2 and OCSL) and markedly rendered cell cycle arrest at G2/M stage. Reversine also induced cell death via both caspase-dependent and -independent apoptosis. In addition, reversine could inhibit Akt/mTORC1 signaling pathway, accounting for its ability to induce autophagy. Conclusions: Taken together, reversine suppresses growth of OSCC via multiple mechanisms, which may be a unique advantage for developing novel therapeutic regimens for treatment of oral cancer in the future. http://www.jbiomedsci.com/content/19/1/9 Ying-Ray Lee Wei-Ching Wu Wen-Tsai Ji Jeff Yi-Fu Chen Ya-Ping Cheng Ming-Ko Chiang Hau-Ren Chen Journal of Biomedical Science 2012, null:9 2012-01-27T00:00:00Z doi:10.1186/1423-0127-19-9 /content/figures/1423-0127-19-9-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 9 2012-01-27T00:00:00Z PDF Background: One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid beta protein (Abeta) within lesions known as senile plaques. Abeta is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Abeta that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a beta-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As gamma-secretase catalyzes the final cleavage that releases the Abeta42 or 40 from amyloid beta -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. gamma-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs gamma-secretase cleavage. Methods: In this study we used RNA interference (RNAi) technology to examine the effects of small-interfering RNA (siRNA) against PS1 on expression levels of PS1 and Abeta42 in IMR-32 Cells using RTPCR, western blotting and immunofluorescence techniques. Results: The results of the present study showed down regulation of PS1 and Abeta42 in IMR32 cells transfected with siRNA against PS1. Conclusion: Our results substantiate the concept that PS1 is involved in gamma-secretase activity and provides the rationale for therapeutic strategies aimed at influencing Abeta42 production. http://www.jbiomedsci.com/content/19/1/2 Ramesh Kandimalla Willayat Wani Binukumar Bk Kiran Gill Journal of Biomedical Science 2012, null:2 2012-01-03T00:00:00Z doi:10.1186/1423-0127-19-2 /content/figures/1423-0127-19-2-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 2 2012-01-03T00:00:00Z PDF Pathogen persistence in immune-competent hosts represents an immunological paradox. Increasing evidence suggests that some pathogens, such as, Leishmania major (L. major) have evolved strategies and mechanisms that actively suppress host adaptive immunity. If this notion is correct conventional vaccination therapies may be ineffective in enhancing host immunity, unless natural processes that suppress host immunity are also targeted therapeutically. The key problem is that the basis of pathogen persistence in immune-competent individuals is unknown, despite decades of intense research. This fact, coupled with poor health care and a dearth of effective treatments means that these diseases will remain a scourge on humans unless a better understanding of why the immune system tolerates such infections emerges from research. Indoleamine 2,3-dioxygenase (IDO) has been shown to act as a molecular switch regulating host responses, and IDO inhibitor drugs shown to possess potential in enhancing host immunity to established leishmania infections. It is hoped that this review will help stimulate and help generate critical new knowledge pertaining to the IDO mechanism and how to exploit it to suppress T cell mediated immunity, thus offer an innovative approach to studying the basis of chronic leishmania infection in mice. http://www.jbiomedsci.com/content/19/1/5 Levi Makala Journal of Biomedical Science 2012, null:5 2012-01-09T00:00:00Z doi:10.1186/1423-0127-19-5 /content/figures/1423-0127-19-5-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 5 2012-01-09T00:00:00Z PDF Background: Fat embolism syndrome (FES) associated with acute lung injury (ALI) is a clinical condition following long bone fracture. We have reported 14 victims due to ALI with FES. Our laboratory has developed an animal model that produced fat emboli (FE). The major purpose of this study was to test whether neutrophil activation with phorbol myristate acetate (PMA) and inhibition with sivelestat (SVT) exert protection on the lung. Methods: The lungs of Sprague-Dawley rats were isolated and perfused. FE was produced by addition of corn oil micelles into the lung perfusate. PMA and SVT were given simultaneously with FE. Parameters such as lung weight/body weight ratio, LW gain, exhaled nitric oxide (NO), protein concentration in bronchoalveolar lavage relating to ALI were measured. The neutrophil elastase (NE), myeloperoxidase, malondialdehyde and phopholipase A2 activity were determined. We also measured the nitrate/nitrite, methyl guanidine (MG), and cytokines. Pulmonary arterial pressure and microvascular permeability were assessed. Lung pathology was examined and scored. The inducible and endothelial NO synthase (iNOS and eNOS) were detected. Results: FE caused ALI and increased biochemical factors. The challenge also resulted in pulmonary hypertension and increased microvascular permeability. The NE appeared to be the first to reach its peak at 1 hr, followed by other factors. Coadministration with PMA exacerbated the FE-induced changes, while SVT attenuated the effects of FE. Conclusions: The FE-induced lung changes were enhanced by PMA, while SVT had the opposite effect. Sivelestat, a neutrophil inhibitor may be a therapeutic choice for patients with acute respiratory distress syndrome (ARDS) following fat embolism. http://www.jbiomedsci.com/content/19/1/3 Chia-Chih Lin Pei-Hsin Liu Shang Jyh Kao Hsing I Chen Journal of Biomedical Science 2012, null:3 2012-01-05T00:00:00Z doi:10.1186/1423-0127-19-3 /content/figures/1423-0127-19-3-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 3 2012-01-05T00:00:00Z XML Background: The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample. Methods: We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke. Results: There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively. Conclusions: This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke. http://www.jbiomedsci.com/content/19/1/1 Yi-Chen Hsieh Sudha Seshadri Wen-Ting Chung Fang-I Hsieh Yi-Hsiang Hsu Huey-Juan Lin Hung-Pin Tseng Li-Ming Lien Chyi-Huey Bai Chaur-Jong Hu Jiann-Shing Jeng Sung-Chun Tang Chin-I Chen Chia-Chen Yu Hung-Yi Chiou Journal of Biomedical Science 2012, null:1 2012-01-03T00:00:00Z doi:10.1186/1423-0127-19-1 /content/figures/1423-0127-19-1-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 1 2012-01-03T00:00:00Z XML Background: Although recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we investigated whether early IPC could upregulate hypoxia inducible transcription factor-1alpha (HIF-1alpha) expression and could reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide (NO) production would abolish these protective effects. Methods: Kidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously injection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results of these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1alpha and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters. Results: IPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1alpha levels as compared to I/R group. Moreover, our results showed that IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial effects of IPC against renal I/R insults. Conclusion: These findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1alpha stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application. http://www.jbiomedsci.com/content/19/1/7 Asma Mahfoudh-Boussaid Mohamed Amine Zaouali Kaouther Hadj-Ayed Abdel-Hedi Miled Dalila Saidane-Mosbahi Joan Rosello-Catafau Hassen Ben Abdennebi Journal of Biomedical Science 2012, null:7 2012-01-17T00:00:00Z doi:10.1186/1423-0127-19-7 /content/figures/1423-0127-19-7-toc.gif Journal of Biomedical Science 1423-0127 ${item.volume} 7 2012-01-17T00:00:00Z PDF