The efficacy of cell transplantation in heart failure is reportedly modest, but adjuvant drugs combined with cell therapy may improve this efficacy. Peroxisome proliferator-activated receptor (PPAR)γ, one of the hypoglycemic medicine for diabetes mellitus, reportedly enhances cytokine production in adipose tissue-derived regenerative cells (ADRCs). We hypothesized that combined administration of PPARγ agonists and ADRCs may enhance the paracrine effects of adiponectin (APN), leading to functional recovery in a chronic myocardial infarction (MI) model.

There is no gold standard indicator that is currently used to predict posthepatectomy liver failure (PHLF). A novel indicator of liver function, the LU15 index of 99mTc-galactosyl serum albumin (GSA) scintigraphy, refers to the liver uptake ratio over a 15-min interval. We aimed to evaluate the usefulness of the future liver remnant (FLR)-LU15 in predicting PHLF. The clinical data of 102 patients (70 males and 32 females; median age, 70 years) who underwent liver resection between January 2011 and August 2019 were analyzed. The FLR-LU15 was calculated by a fusion of simulated 3-dimensional images and 99mTc-GSA scintigraphy. PHLF was determined according to the definition of the International Study Group of Liver Surgery. The FLR-LU15 was an independent risk factor for PHLF ≥ Grade B according to multivariate analysis, and its value correlated with the PHLF grade. The area under the receiver operating characteristic curve of the FLR-LU15 for PHLF ≥ Grade B was 0.816 (95% confidence interval, 0.704-0.929), which was better than that of other indicators. When the cut-off value of FLR-LU15 was set at 16.7, the sensitivity was 86.7%, specificity was 74.7%, and odds ratio was 19.2 (95% confidence interval, 4.0-90.9), all of which were superior to other indicators. If the cut-off value was 13, the positive predictive value was 57.1%. The FLR-LU15 is a useful predictor of PHLF and may be more reliable than other predictors.

Oxidative stress has been suggested as a mechanism underlying skin aging, as it triggers apoptosis in various cell types, including fibroblasts, which play important roles in the preservation of healthy, youthful skin. Catechins, which are antioxidants contained in green tea, exert various actions such as anti-inflammatory, anti-bacterial, and anti-cancer actions. In this study, we investigated the effect of (+)-catechin on apoptosis induced by oxidative stress in fibroblasts.

In cutaneous T-cell lymphoma (CTCL), which arises from skin-tropic memory T cells, malignant T cells and benign T cells are confined in the same skin lesions. It is thus difficult to evaluate the phenotypic characteristics and functional activities of benign T cells in CTCL. Disialoganglioside with three glycosyl groups (GD3) is increasingly expressed on the surface of solid malignant tumor cells and takes part in tumor progression and suppression of tumor immunity. However, the role of GD3 in CTCL is not well-understood. In this study, the malignant and benign T cells in CTCL skin lesions were distinguished by flow cytometry and their phenotypic characteristics were compared with those of T cells from control skin specimens. In CTCL skin lesions, the benign T cells included limited resident memory T cells (TRM), which are sessile in skin and known to exert strong antitumor function. The benign T cells showed diminished Th17 property, and the expression of GD3 was high in the malignant T cells. The expression of GD3 in the malignant T cells inversely correlated with IL-17A production from the benign CD4 T cells. GD3 from the malignant T cells was implied to be involved in suppressing the Th17 activity of the benign T cells independent of the regulation of TRM differentiation in CTCL. Revealing the role of GD3 in inhibiting the production of IL-17A in CTCL would aid the understanding of the suppressive mechanism of the antitumor activity by malignant tumor cells.

Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC.

Pluripotent stem cells are used in regenerative medicine and exist in various internal organs. However, there are a small number of reports of neural cells or neural stem cells existing in the spleen. In this study, we sought to identify possible neural stem cells in the mouse spleen. The spleens of ICR mice were removed and small specimens were incubated in Dulbecco's modified Eagle's medium with Nutrient Mixture F-12 containing either 10% fetal bovine serum (FBS), 20% FBS, 10% neonate bovine serum, or 10% fetal calf serum. Neural cell medium was also used. The cultured cells were investigated for expression of the neural cell markers neuron-specific enolase (NSE) and neurofilament 150 kDa (NF-150) by immunocytochemistry. Mouse spleens were also examined by immunohistochemistry for NSE, NF-150, NF-200, peripherin, and glial fibrillary acidic protein. Cells morphologically resembling neural cells were obtained and were positive for neural cell markers. Some of the cells generated sphere-like formations, which may have been neurospheres. Cell proliferation was best in medium containing 10% FBS. Cells positive for neural markers were observed in the subcapsular and perivascular regions of the spleen. The cells were round and present in much lower numbers than in cell culture. These cells are suspected neural stem cells and would be expected to differentiate into neural cells in cell culture. This report suggests the existence of neural stem cells in the mouse spleen.

Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory-motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons.

Secondary reconstruction after breast-conserving surgery is generally challenging because of the nature of irradiated tissue. The aim of this study was to validate the use of latissimus dorsi myocutaneous (LDM) flaps for secondary breast reconstruction after breast-conserving surgery.

Although there have been many reports on the success of free jejunal flap transfer for pharyngoesophageal reconstruction, reports on salvage procedures for failed transfers remain sparse. In this report, we retrospectively reviewed our salvage procedures for failed jejunal transfers and previous articles describing salvage treatment in failed jejunal flap cases.

Hydrogen is effective against ischemia-reperfusion (I/R) injury in skin flaps. However, the difficulty of continuously administering a sufficient amount of hydrogen using conventional methods has been an issue in the clinical application of hydrogen-based therapy. An Si-based agent administered orally was previously shown to continuously generate a large amount of hydrogen in the intestinal environment. In this study, we assessed the effect of the Si-based agent on the inhibition of I/R injury in skin flaps using a rat model. In the I/R groups, the vascular pedicle of the abdominal skin flap was occluded for three hours followed by reperfusion. In the I/R + Si group, the Si-based agent was administered perioperatively. After reperfusion, flap survival rate, blood flow, oxidative stress markers, inflammatory markers/findings, and degree of apoptosis were evaluated. Flap survival rate was significantly higher, and histological inflammation, apoptotic cells, oxidative stress markers, and levels of inflammatory cytokine mRNA and protein expression were significantly lower, in the I/R + Si group compared to the I/R group. The Si-based agent suppressed oxidative stress, apoptosis, and inflammatory reactions resulting from I/R injury, thereby contributing to improvements in skin flap survival.

Although HOXB9 induces tumor proliferation and chemoresistance in several cancer cells, little is known in pancreatic ductal adenocarcinoma (PDAC). In the present study, increased expression of HOXB9 in PDAC was associated with the induction of angiogenic factors and poor overall survival through the TGFβ pathway. Taken together, these results suggested that HOXB9 expression in PDAC could be a surrogate marker in clinical treatment.

Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207-1216.