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The goal of surgery for degenerative spine disease is to decompress nerves; however, extensive spinal decompression may compromise spinal stability. Therefore, spinal fusion surgery is performed to immediately stabilize such anatomical disruption during a short hospital stay and to allow quick recuperation. Recently, implants such as pedicle screws and intervertebral cages have been regularly used in lumbar fusion surgery. These implants are used to reconstruct the functional unit of the failed spine, correcting any deformity if necessary and maintaining its fixation until complete bone fusion. In other words, the essence of spinal fusion surgery is not the placement of implants but the induction of bone fusion. Therefore, each case requires a carefully developed surgical plan to achieve sufficient bone fusion for spinal stabilization. In this article, we describe the mechanism and the surgical technique for achieving reliable interbody fusion.

Extract of Cyclolepis genistoides D. Don (vernacular name Palo azul; Palo) are traditionally consumed in the Republic of Paraguay in South America for the treatment of diabetes and kidney disease, and is sold in Japan as dietary supplement. This study aimed to elucidate the mechanism of anti-diabetes activity of Palo, especially focused on insulin resistance. Palo promoted adipocytes differentiation and regulated adipokine profiles in 3T3-L1 adipocytes by modulation of PPARγ, a major regulator of adipose differentiation. Human adipocyte showed almost similar profile with 3T3-L1 against Palo treatment. Furthermore, Palo treatment (250 or 1000 mg/kg) was performed with C57BL/6J mice for 14 weeks, being fed high-fat-diet (HFD60) simultaneously. Palo 250 mg/kg exhibited a tendency to decrease subcutaneous adipose volume along with increase of PPARγ and its target, adiponectin mRNA expression. In addition, as the other insulin targeted cell, effect on muscle differentiation was examined. Palo increased differentiation of C2C12 mouse muscle myoblasts by increase of IGF-1, myogenin, and myosine heavy chain (MHC) as well as 5'-AMP-activated protein kinase (AMPK) activation. Palo subsequently promoted myotube formation under differentiation condition. From the above, it was clarified that Palo acts variously on the differentiation and maturation of both adipocytes and muscle cells, and from the viewpoint of the regulatory mechanism for adipocytes, PPARγ-inducing action was shown to be a mechanism that acts across species.

Although protein replacement is an effective treatment for serum protein deficiencies such as diabetes and hemophilia, recombinant protein products are not available for all rare inherited diseases due to the instability of the recombinant proteins and/or to cost. Gene therapy is the most attractive option for treating patients with such rare diseases. To develop an effective ex vivo gene therapy-based protein replacement treatment requires recipient cells that differ from those used in standard gene therapy, which is performed to correct the function of the recipient cells. Adipose tissue is an expected source of proliferative cells for cell-based therapies, including regenerative medicine and gene transfer applications. Based on recent advances in cell biology and extensive clinical experience in transplantation therapy for adipose tissue, we focused on the mature adipocyte fraction, which is the floating fraction after collagenase digestion and centrifugation of adipose tissue. Proliferative adipocytes were propagated from the floating fraction by the ceiling culture technique. These cells are designated as ceiling culture-derived proliferative adipocytes (ccdPAs). We first focused on lecithin:cholesterol acyltransferase (LCAT) deficiency, an inherited metabolic disorder caused by lcat gene mutation, and ccdPAs as a therapeutic gene vehicle for LCAT replacement therapy. In our recent in vitro and animal model studies, we developed an adipose cell manipulation procedure using advanced gene transduction methods and transplantation scaffolds. We herein introduce the progress made in novel adipose tissue-based therapeutic strategies for the treatment of protein deficiencies and describe their future applications for other intractable diseases.

In this communication, we report a patient with familial amyotrophic lateral sclerosis (ALS) associated with a familial dyslipidemia. Genetic analysis revealed a novel heterozygous valosin-containing protein (VCP) mutation (c.466G>T (p.G156C)). The other gene analysis also disclosed a known homozygous LCAT mutation (c.101C>T (p.P10L)). VCP gene mutation shown should be responsible for familial ALS because of following reasons. The patient's father also was also affected by ALS. The VCP gene mutation (p.G156C) in the patient was located in the vicinity of a site frequently associated with pathogenic VCP variants. The same amino acid transformation as that of this patient has been reported to be involved in the pathogenesis of inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia. This is the first case report of rare association of ALS with VCP mutation and dyslipidemia with LCAT mutation.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), a latent viral protein consistently expressed in infected proliferating cells, is essentially required in trans to maintain EBV episomes in cells. Thus EBNA1 will be an appropriate target for specific molecular therapy against EBV-associated cancers. We constructed a mutant (mt) EBNA1 lacking the N-terminal-half, relative to wild-type (wt) EBNA1, and demonstrated that it exerted dominant-negative effects on maintenance of the viral episome from cells regardless of viral latency or tissue origin thereby leading to significant suppression of naturally EBV-harboring Burkitt's lymphoma cell growth in vitro and in vivo. Our mutant can act as dominant-negative (dn) EBNA1 and will afford an additional therapeutic strategy specifically targeting EBV-associated malignancies. The similar approach can be applicable to exploit novel remedial protocols against uncontrollable diseases caused by other persistently-infected viruses. In addition, dnEBNA1 may also provide a useful analytical tool for the possible oncogenic function(s) of wtEBNA1.