BioMedicine RSS feed: Articles in Press. BioMedicine is a peer-reviewed journal that aims to publish high quality scientific research in the field of translational and personalized medicine, with the goal of promoting and disseminating medical science knowledge to improve global health. It is published quarterly by Elsevier. Articles on clinical, laboratory and social research in translational and personalized medicine and other related fields that are of interest to the medical profession are eligible for consideration. Review articles, original articles, case reports, short communications, and letters to the editor are accepted. http://www.e-biomedicine.com//inpress?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. BioMedicine2211-80202012-05-11 © 2012 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.e-biomedicine.com/article/PIIS2211802012000319/abstract?rss=yesSummary: Deranged metabolism of low-density lipoprotein (LDL) is considered the preeminent modifiable risk factor for atherosclerotic disease, widely viewed as a chronic inflammatory disorder. Yet the search for a circulating atherogenic LDL species continues, as risk of coronary artery disease (CAD) cannot be measured by absolute LDL cholesterol concentrations in the plasma. Oxidized LDL (oxLDL) and small, dense LDL are associated with CAD, but neither has been retrieved from human plasma to undergo mechanistic scrutiny. Electronegative LDL, a subclass of human plasma LDL, exhibits atherogenic properties in cultured vascular cells. L5, the most negatively charged subfraction of LDL, is an extreme form of electronegative LDL that we isolated through anion-exchange chromatograpgy in plasma of patients with higher cardiac risk (active smoking, hypercholesterolemia, type 2 diabetes mellitus, metabolic syndrome). L5, scant in healthy normal subjects, is as potent as artificially prepared oxLDL in inducing endothelial cell (EC) apoptosis by means of disrupting fibroblast growth factor 2 (FGF2) autoregulation that involves protein kinase Akt. Unlike oxLDL, however, L5 is not oxidized. Among subfractions L1-L5, separated by our chromatographic method, L1 is the most abundant and least negatively charged. It represents harmless normal LDL. Compared to L1, L5 has greater content of total protein and triglycerides but a lesser amount of cholesteryl esters. Assays by size exclusion chromatography and equilibrium density gradient ultracentrifugation determine L5 as neither smaller nor denser than L1. Negative charge on the particle surface has made L5 unrecognizable by the normal LDL receptor. Instead, L5 signals through and is internalized by lectin-like oxidized LDL receptor-1 (LOX-1), which has high affinity for negatively charged ligands. LOX-1 is also inducible by L5 but not L1. Through LOX-1, L5 disturbs homeostasis between the prosurvival and proapoptosis members of the Bcl-2 family, leading to mitochondrial destabilization. Additionally, it induces overexpression of various adhesion molecules and chemokines, thus promoting monocyte-EC adhesion, an early event during atherosclerosis development. Endothelial progenitor cells (EPCs) are important construction units for vascular repair and endothelial regeneration. To add to the damage, L5 impairs EPC differentiation from mononuclear cells by inhibiting induction of needed growth factor receptors. It also accelerates EPC senescence by suppressing the enzymatic activity of telomerase essential for chromosome preservation. Thus, L5 is a naturally occurring, negatively charged but not oxidized LDL entity, neither smaller nor denser than normal LDL, but possessing a capacity for inducing a spectrum of atherogenic responses in vascular cells. Further investigation aimed at establishing its clinical relevance is warranted to confirm its atherogenic role. Subsequent efforts in L5 research will be directed toward development of new diagnostic and treatment methods for CAD and other ischemic vascular diseases.Negatively charged L5 as a naturally occurring atherogenic low-density lipoprotein - Accepted ManuscriptGuei-Jane Wang, Chiz-Tzung Chang, Chao-Yuh Yang, Chu-Huang Chen10.1016/j.biomed.2012.05.003BioMedicine (2012)2012-05-11BioMedicine2012-05-11REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS2211802012000307/abstract?rss=yesAbstract: Amyotrophic lateral sclerosis (ALS) is a rare and lethal neurodegenerative disease for which there is no effective medical treatment. Although riluzole, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be reasonably safe for patients with ALS, the drug has been demonstrated to prolong median survival by only two to five months. There is mounting evidence that stem cell-based gene therapy is a promising treatment modality for patients with ALS. In this review, we focus on the types, sources, and doses of stem cells that have been shown to be effective for ALS patients, the differences in cytokines or chemokines secreted from these various stem cells, and the immune-modulation activity of stem cells as treatment for ALS.Stem Cell Therapy in ALS - Accepted ManuscriptKuo-Wei Hsueh, An-Chang Hsieh, Horng-Jyh Harn, Shinn-Zong Lin10.1016/j.biomed.2012.05.002BioMedicine (2012)2012-05-10BioMedicine2012-05-10REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS2211802012000289/abstract?rss=yesAbstract: Acupuncture including moxibustion is an ancient medicine, it is used to treat disease had been at least two thousands in China. Throughout two thousands develops, the acupuncture had been accepted widely in the Western countries. World Health Organization conducted a symposium and list 40 suitable diseases for acupuncture in 1979. The acupuncture as a tool to treat disease is very popular in the Taiwan, particularly for nervous systemic disease including stroke, dementia, Parkinson’s disease, headache, epilepsy, Bell’s palsy and carpal tunnel syndrome etc., but the efficacy of the acupuncture remain unclear, therefore, the aim of the present study was to review the articles whether the existing enough evidence to support beneficial effect of acupuncture. The results indicated that the acupuncture treatment is beneficial including subacute and chronic stage of stroke for muscle spasticity, migraine prophylaxis, tension type headache, Bell’s palsy and carpal tunnel syndrome; the efficacy of the acupuncture need more evidence including acute stage of stroke for motor function, dementia including Alzheimer’s disease, vascular dementia, Parkinson’s disease and epilepsy etc.Acupuncture in nervous systemic disease - Accepted ManuscriptChing-Liang Hsieh10.1016/j.biomed.2012.04.004BioMedicine (2012)2012-05-07BioMedicine2012-05-07REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS2211802012000277/abstract?rss=yesAbstract: Obsessive compulsive disorder (OCD) is a prevalent and debilitating illness that often follows a chronic course. Up to 40% of OCD patients received little or no benefit from currently available pharmacotherapy or exposure-based behavior psychotherapy. Thus, there is an urgent need to develop new strategies for the treatment of OCD. Although the neurobiology and etiology of OCD are not completely understood, growing clinical and preclinical evidence appears to support the abnormalities of glutamatergic neurotransmission, including N-methyl-D-aspartate subtype receptor (NMDAR) function, in the pathophysiology and treatment of OCD. This review summarizes the findings from neuro imaging, candidate genes, animal models, and treatment studies in the context of glutamatergic dysregulation, with particular emphasis on the synaptic NMDAR function. The converging evidence indicates the potential of glutamate-modulating agents in the development of novel treatment for OCD.Glutamate theory in developing novel pharmacotherapies for obsessive compulsive disorder: Focusing on N-methyl-D-aspartate signaling - Uncorrected ProofPo-Lun Wu, Hsien-Yuan Lane, Hwa-Sheng Tang, Guochuan E. Tsai10.1016/j.biomed.2012.04.003BioMedicine (2012)2012-04-27BioMedicine2012-04-27REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS2211802012000265/abstract?rss=yesAbstract: In encephalopathic infants, cerebrospinal fluid hyperglycinemia and elevated cerebrospinal fluid to plasma glycine ratio are considered pathognomonic of nonketotic hyperglycinemia (NKH). We present a case of NKH complicated by neonatal intractable seizures. Increased ratio of cerebrospinal fluid to plasma glycine concentrations of 0.28 was seen as a strong diagnostic indicator of nonketotic hyperglycinemia. Evaluating sick neonates with hypotonia, encephalopathy, and/or seizures is a diagnostic challenge. NKH should be considered; elevated cerebrospinal fluid/plasma glycine ratio will allow correct identification and treatment more often in the future.Nonketotic hyperglycinemia: A case report and brief review - Corrected ProofYu-Tzu Chang, Wei-De Lin, Zheng-Nan Chin, Chung-Shing Wang, I.-Ching Chou, Huang-Tsung Kuo, Fuu-Jen Tsai10.1016/j.biomed.2012.04.002BioMedicine (2012)2012-04-23BioMedicine2012-04-23CASE REPORThttp://www.e-biomedicine.com/article/PIIS2211802012000253/abstract?rss=yesA 12-year-old girl, presented to the Outpatient Department with congenital non- progressive cranial-facial-digital abnormalities and normal developmental milestones, had a past medical history of congenital heart disease (atrial septal defect, tricuspid valve regurgitation) under long-term follow-up. Clinically, specific phenotype was characterized by widely separated eyes (hypertelorism), broad nasal root, bifid nasal tip, clinodactyly over left 5th finger and slim fingers (Panel A,B and C). Computed tomography of her head revealed no skull asymmetry or brachycephaly (Panel D). Her mother showed similar characteristics but with facial asymmetry (Panel E) due to isolated right coronal suture craniosynostosis that had received surgical correction. Although craniofrontonasal dysplasia was our first impression of diagnosis according to the index case's clinical manifestations, mode of inheritance (most likely autosomal dominant or X-linked dominant disorder) and a hint of isolated craniosynostosis from her mother, several disorders having similar symptoms to those of craniofrontonasal dysplasia, including Aarskog syndrome (widely spaced eyes and broad nose; but lack of low-set ear, short, broad hands with stubby hands, genital malformations and mental retardation), Frontonasal dysplasia (for her hypertelorism, broad nose, vertical grove down the tip of the nose; fall short of nose split into two, brachycephaly, cleft lip and/or palate, microphthalmia and mental retardation; sporadic occurrence), Frontofacionasal dysplasia (wide space between the eyes, no cleft lip and/or palate, telecanthus, brachycephaly, mid-face hypoplasia; autosomal recessive inheritance), Greig cephalopolysyndactyly syndrome (widely separated eyes; but no prominent forehead, polydactyly and/or syndactyly) and a variety of craniosynostosis (not seen in this index patient, but her mother had prematurely closed right coronal skull suture) syndromes, should be on the list of differential diagnoses. Craniofrontonasal dysplasia has an X-linked dominant inheritance mode. Direct sequencing of all exons and exon-intron boundaries of the EFNB1 gene subsequently revealed C-to-G transversion at nucleotide 354 in exon 2 [EFNB1 (Xq12), exon2: c.354C>G, p.S118R] (Panel F). This disease-causing novel mutation was inherited from her mother with intrafamilial phenotypic variability. Craniofrontonasal dysplasia is inherited as an X-linked dominant pattern. A female inherits one X chromosome from each parent, while a male gets an X chromosome from the mother and a Y from the father. The male thus displays X-linked trait from the mother, while a female may have X-linked traits from either parent. Because of dominantly inherited pattern, only one copy of defective gene EFNB1 is necessary for the disease to appear. No definite therapy for craniofrontonasal dysplasia is available so far, except for plastic surgery.Craniofacial dysmorphism, what is your diagnosis? - Corrected ProofChung-Hsing Wang, Wei-De Lin, Fuu-Jen Tsai10.1016/j.biomed.2012.04.001BioMedicine (2012)2012-04-12BioMedicine2012-04-12CLINICAL SPOTLIGHThttp://www.e-biomedicine.com/article/PIIS2211802012000241/abstract?rss=yesAbstract: Traditional Chinese Medicine (TCM) is widely used in clinical research due to its low toxicity, low number of side effects, and low cost. Many components of common fruits and vegetables play well-documented roles as chemopreventive or chemotherapeutic agents that suppress tumorigenesis. Anthraquinones are commonly extracted from the Polygonaceae family of plants, e.g., Rheum palmatum and Rheum officinale. Some of the major chemical components of anthraquinone and its derivatives, such as aloe-emodin, danthron, emodin, chrysophanol, physcion, and rhein, have demonstrated potential anticancer properties. This review evaluates the pharmacological effects of emodin, a major component of Aloe vera. In particular, emodin demonstrates anti-neoplastic, anti-inflammatory, anti-angiogenesis, and toxicological potential for use in pharmacology, both in vitro and in vivo. Emodin demonstrates cytotoxic effects (e.g., cell death) through the arrest of the cell cycle and the induction of apoptosis in cancer cells. The overall molecular mechanisms of emodin include cell cycle arrest, apoptosis, and the promotion of the expression of hypoxia-inducible factor 1α, glutathione S-transferase P, N-acetyltransferase, and glutathione phase I and II detoxification enzymes while inhibiting angiogenesis, invasion, migration, chemical-induced carcinogen-DNA adduct formation, HER2/neu, CKII kinase, and p34cdc2 kinase in human cancer cells. Hopefully, this summary will provide information regarding the actions of emodin in cancer cells and broaden the application potential of chemotherapy to additional cancer patients in the future.Anticancer potential of emodin - Corrected ProofShu-Chun Hsu, Jing-Gung Chung10.1016/j.biomed.2012.03.003BioMedicine (2012)2012-04-06BioMedicine2012-04-06REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS221180201200023X/abstract?rss=yesAbstract: Increasing evidence suggests that inflammation responses play an important role in the pathophysiology of depression. Clinically depressed patients manifest higher levels of inflammatory biomarkers, while proinflammatory cytokines induce neuropsychiatric symptoms (sickness behavior) as well as major depressive episode. Mechanisms that might be responsible for inflammation-mediated neuropsychiatric and depressive symptoms are vital in understanding “mind–body” interface; these have been studied in clinical and animal models (e.g., interferon-α-induced depression in patients with chronic hepatitis C, one of the most notable clinical models for testing inflammation theory of depression and an excellent approach to investigate development of depression in a prospective manner). Furthermore, the anti-inflammatory pathway has become a hot topic in looking for new antidepressant therapies. Recently, omega-3 polyunsaturated fatty acids (omega-3 PUFAs or n-3 PUFAs) have gained more attention as a promising treatment for depression. raEicosapentanoic acid and docosahexanoic acid, major bioactive components of omega-3 PUFAs, are both natural anti-inflammatory and antidepressant agents. Here, we review recent epidemiological studies, cross-sectional and longitudinal case-controlled studies, interventional clinical trials, as well as basic animal and cellular studies to prove the linkage among omega-3 PUFAs, inflammation, and depression.Inflammation in psychopathology of depression: Clinical, biological, and therapeutic implications - Corrected ProofKuan-Pin Su10.1016/j.biomed.2012.03.002BioMedicine (2012)2012-03-29BioMedicine2012-03-29REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS2211802012000228/abstract?rss=yesAbstract: Spinal reflex potentiation (SRP) in the pelvic-urethra reflex activity is a form of activity-dependent neural plasticity, presumed to be essential for urethra contraction resulting continence under physiological conditions and also to underlie the pelvic pain caused by pathology in the pelvic cavity. Studies have demonstrated that SRP could be induced by electrical shocks, bladder distension and activation of the lumbosacral (L6-S1) spinal glutamatergic NMDA and AMPA receptors. Conversely, blockage of glutamatergic receptors using selective antagonists either attenuated or abolished the established SRP. Electrical shocks on and nicotine microinjection into the pontine tegmentum area facilitated SRP induction, but intrathecal serotonin antagonists abolished electrical stimulation- and nicotine-induced facilitation on SRP. Finally, the induction of SRP is highly estrogen-dependent, because surgical ablation of menstruation diminished the SRP which is prevented by estradiol supplements, and SRP is more significant in proestrus (high estrogen but low progesterone) than in metestrus (both estrogen and progesterone are low) of the menstrual cycle. We propose that SRP is relevant to urine continence under physiological conditions, and pathological facilitation of SRP could result in pelvic pain.Spinal pelvic-urethra reflex potentiation - Corrected ProofHsien-Yu Peng, Tzer-Bin Lin10.1016/j.biomed.2012.03.001BioMedicine (2012)2012-03-26BioMedicine2012-03-26REVIEW ARTICLEhttp://www.e-biomedicine.com/article/PIIS2211802012000046/abstract?rss=yesAbstract: Chondrosarcoma is highly malignant, with a strong capacity for local invasion as well as distant metastasis. Surgical resection remains the primary mode of therapy. This cancer shows a predilection for metastasis to the lungs. This article will highlight numerous molecular mechanisms mediating cell motility, as described in such cases. Numerous experiments have demonstrated that upregulation of integrin and matrix metalloproteinases (MMPs) and intercellular adhesion molecule-1 (ICAM-1) expression lead to increased tumor cell migration and invasion. Data from these experiments suggest that targeting these pathways and molecules may enhance control of chondrosarcoma and decrease metastasis ratio.Molecular mechanisms of chondrosarcoma metastasis - Corrected ProofChih-Hsin Tang10.1016/j.biomed.2012.01.001BioMedicine (2012)2012-02-16BioMedicine2012-02-16REVIEW ARTICLE