Aggressive fibromatosis of the sigmoid colon: A case report.

BACKGROUND: Aggressive fibromatosis (AF), also known as desmoid tumor or desmoid-type fibromatosis, is a rare soft tissue neoplasm that can occur in almost any part of the body. Although it is a benign disease, AF is aggressive and infiltrative and has a high recurrence rate after surgery. Common sites for intra-abdominal AF are the small bowel mesentery, retroperitoneum, and pelvis. AF in the colon is extremely rare. CASE SUMMARY: Here, we report the first case of sigmoid colon AF, which was accidentally discovered in a 27-year-old woman during laparoscopic myomectomy. Computed tomography confirmed a slightly enhanced mass in the sigmoid colon. Subsequent colonoscopy did not reveal a mass in the colonic lumen, but a suspected external compress was found in the sigmoid colon. Surgical disease involving a gastrointestinal stromal tumor was suspected. The patient underwent laparoscopic exploration, and sigmoidectomy with a negative margin was performed to excise the mass. Postoperative immunohistochemistry revealed that the mass was an AF. The patient recovered well and was recurrence-free at the 30-month follow-up without adjuvant therapy. CONCLUSION: AF should be considered in the differential diagnosis of subepithelial colon masses. Radical resection alone can achieve good outcomes.

Controllable Microparticle Spinning via Light without Spin Angular Momentum.

The spin angular momentum (SAM) of an elliptically or circularly polarized light beam can be transferred to matter to drive a spinning motion. It is counterintuitive to find that a light beam without SAM can also cause the spinning of microparticles. Here, we demonstrate controllable spinning of birefringent microparticles via a tightly focused radially polarized vortex beam that has no SAM prior to focusing. To this end, the orbital Hall effect is proposed to control the radial separation of two spin components in the focused field, and tunable transfer of local SAM to microparticles is achieved by manipulating the twisted wavefront of the source light. Our work broadens the perspectives for controllable exertion of optical torques via the spin-orbit interactions.

Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair.

The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain. In many cases, the microenvironment surrounding demyelination lesions contains inhibitory molecules, which lead to repair failure. Accordingly, blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination. In the central nervous system, oligodendrocytes form the myelin sheath. We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation. Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin's pro-proliferation function. Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation, as well as PI3K signaling pathways that are needed in the mid-late stages. When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination, it enhanced myelin regeneration and promoted motor function recovery. These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.

Astrocyte-derived hepcidin controls iron traffic at the blood-brain-barrier via regulating ferroportin 1 of microvascular endothelial cells.

Brain iron dysregulation associated with aging is closely related to motor and cognitive impairments in neurodegenerative diseases. The regulation of iron traffic at the blood-brain barrier (BBB) is crucial to maintain brain iron homeostasis. However, the specific mechanism has not been clarified in detail. Using various conditional gene knockout and overexpression mice, as well as cell co-culture of astrocyte and bEND.3 in the transwell, we found that astrocyte hepcidin knockdown increased the expression of ferroportin 1 (FPN1) of brain microvascular endothelial cells (BMVECs), and that it also induced brain iron overload and cognitive decline in mice. Moreover, BMVECs FPN1 knockout decreased iron contents in the cortex and hippocampus. Furthermore, hepcidin regulates the level of FPN1 of BMVECs with conditional gene overexpression in vivo and in vitro. Our results revealed that astrocytes responded to the intracellular high iron level and increased the secretion of hepcidin, which in turn diminished iron uptake at BBB from circulation through directly regulating FPN1 of BMVECs. Our results demonstrate that FPN1 of BMVECs is a gateway for iron transport into the brain from circulation, and the controller of this gateway is hepcidin secreted by astrocyte at its endfeet through physical contact with BMVECs. This regulation is indeed the major checkpoint for iron transport from the blood circulation to the brain. This study delineates the pathway and regulation of iron entry into the brain, providing potential therapeutic targets for iron dysregulation-related neurological diseases.

Millifolide A, a dimeric ether of degraded sesquiterpene lactones, inhibited the proliferation of human lung cancer cell line A549.

The inhibitory effect of three degraded sesquiterpene lactones, iso-seco-tanapartholide, arteludooicinolide A and millifolide A isolated from Achillea millefolium L., on anti-human lung cancer cells was examined using MTT and reporter gene assays. Millifolide A has significant inhibitory effects on the proliferation of human lung cancer cells probably through inducing cell apoptosis.

Increasing 28 mitogenomes of Ephemeroptera, Odonata and Plecoptera support the Chiastomyaria hypothesis with three different outgroup combinations.

BACKGROUND: The phylogenetic relationships of Odonata (dragonflies and damselflies) and Ephemeroptera (mayflies) remain unresolved. Different researchers have supported one of three hypotheses (Palaeoptera, Chiastomyaria or Metapterygota) based on data from different morphological characters and molecular markers, sometimes even re-assessing the same transcriptomes or mitochondrial genomes. The appropriate choice of outgroups and more taxon sampling is thought to eliminate artificial phylogenetic relationships and obtain an accurate phylogeny. Hence, in the current study, we sequenced 28 mt genomes from Ephemeroptera, Odonata and Plecoptera to further investigate phylogenetic relationships, the probability of each of the three hypotheses, and to examine mt gene arrangements in these species. We selected three different combinations of outgroups to analyze how outgroup choice affected the phylogenetic relationships of Odonata and Ephemeroptera. METHODS: Mitochondrial genomes from 28 species of mayflies, dragonflies, damselflies and stoneflies were sequenced. We used Bayesian inference (BI) and Maximum likelihood (ML) analyses for each dataset to reconstruct an accurate phylogeny of these winged insect orders. The effect of outgroup choice was assessed by separate analyses using three outgroups combinations: (a) four bristletails and three silverfish as outgroups, (b) five bristletails and three silverfish as outgroups, or (c) five diplurans as outgroups. RESULTS: Among these sequenced mitogenomes we found the gene arrangement IMQM in Heptageniidae (Ephemeroptera), and an inverted and translocated tRNA-Ile between the 12S RNA gene and the control region in Ephemerellidae (Ephemeroptera). The IMQM gene arrangement in Heptageniidae (Ephemeroptera) can be explained via the tandem-duplication and random loss model, and the transposition and inversion of tRNA-Ile genes in Ephemerellidae can be explained through the recombination and tandem duplication-random loss (TDRL) model. Our phylogenetic analysis strongly supported the Chiastomyaria hypothesis in three different outgroup combinations in BI analyses. The results also show that suitable outgroups are very important to determining phylogenetic relationships in the rapid evolution of insects especially among Ephemeroptera and Odonata. The mt genome is a suitable marker to investigate the phylogeny of inter-order and inter-family relationships of insects but outgroup choice is very important for deriving these relationships among winged insects. Hence, we must carefully choose the correct outgroup in order to discuss the relationships of Ephemeroptera and Odonata.

Human adipose tissue- and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?

Multiple types of stem cells have been proposed for the treatment of spinal cord injury, but their comparative information remains elusive. In this study, a rat model of T10 contusion spinal cord injury was established by the impactor method. Human umbilical cord-derived mesenchymal stem cells (UCMSCs) or human adipose tissue-derived mesenchymal stem cells (ADMSCs) (2.5 µL/injection site, 1 × 105 cells/µL) was injected on rostral and caudal of the injury segment on the ninth day after injury. Rats injected with mesenchymal stem cell culture medium were used as controls. Our results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo, both significantly improved motor and sensory function. After spinal cord injury, UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration, decreased glial scar and lesion cavity formation, and reduced numbers of active macrophages. Bio-Plex analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factor α in the ADMSC group, as well as a downregulation of macrophage inflammatory protein 3α in both UCMSC and ADMSC groups at 3 days after cell transplantation. Upregulation of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell transplantation. Isobaric tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration, neurotrophy, and cell apoptosis in common and specific manners. In conclusion, UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal growth. However, there were some differences in cytokine and gene expression induced by these two types of transplanted cells. Animal experiments were approved by the Laboratory Animal Ethics Committee at Jinan University (approval No. 20180228026) on February 28, 2018, and the application of human stem cells was approved by the Medical Ethics Committee of Medical College of Jinan University of China (approval No. 2016041303) on April 13, 2016.

Trapping and Manipulation of Single Cells in Crowded Environments.

Optical tweezers provide a powerful tool to trap and manipulate living cells, which is expected to help people gain physiological insights at single-cell level. However, trapping and manipulating single cells under crowded environments, such as blood vessels and lymph nodes, is still a challenging task. To overcome this issue, an annular beam formed by the far-field Bessel beam is introduced to serve as an optical shield to isolate the target cells from being disturbed. With this scheme, we successfully trapped and manipulated single blood cells in a crowded environment. Furthermore, we demonstrated manipulation of two lymphocytes ejected from a lymph node independently with dual-trap optical tweezers, which paves the way for exploring cell interactions under living conditions. Such technique might be helpful in the study of how natural killer cells response to virus-infected cells or cancer cells.

Ceruloplasmin, a Potential Therapeutic Agent for Alzheimer's Disease.

AIMS: Ceruloplasmin (CP), a ferrous oxidase enzyme, plays an important role in regulating iron metabolism and redox reactions. Previous studies showed that CP deficiency contributes to Parkinson's disease by increasing iron accumulation and oxidative stress in the substantia nigra. However, the role of CP in Alzheimer's disease (AD) is unclear. We hypothesized that the lack of CP gene expression would affect the pathogenesis and damage of AD by promoting abnormal iron levels and oxidative stress. RESULTS: AD mouse models were induced in CP knockout mouse either by injection of Aß25-35 into the lateral ventricle of the brain or transgenic APP expression. CP levels were decreased significantly in the hippocampus of AD patients, as well as Aß-CP+/+ and APP-CP+/+ mice. Compared to control AD mice, CP gene deletion increased memory impairment and iron accumulation, which could be associated with elevated reactive oxygen species (ROS) levels and lead to cell apoptosis mediated through the Bcl-2/Bax and Erk/p38 signaling pathways in Aß-CP-/- and APP-CP-/- mice. In contrast, the restoration of CP expression to CP-/- mice through injection of an exogenous expression plasmid into the brain ventricle alleviated Aß-induced neuronal damage in the hippocampus. INNOVATION: CP alterations in iron contents were mediated through DMT1(-IRE) and changes in ROS levels, which in turn attenuated the progression of AD through the Erk/p38 and Bcl-2/Bax signaling pathways. CONCLUSION: Our results show a protective role of CP in AD and suggest that regulating CP expression in the hippocampus may provide a new neuroprotective strategy for AD. Antioxid. Redox Signal. 28, 1323-1337.

Stability and cytotoxicity of angiotensin-I-converting enzyme inhibitory peptides derived from bovine casein.

This study investigated the effect of heat treatment combined with acid and alkali on the angiotensin-I-converting enzyme (ACE) inhibitory activity of peptides derived from bovine casein. The free amino group content, color, and cytotoxicity of the peptides were measured under different conditions. When heated at 100 °C in the pH range from 9.0 to 12.0, ACE inhibitory activity was reduced and the appearance of the peptides was significantly darkened. After thermal treatment in the presence of acid and alkali, the free amino group content of ACE inhibitory peptides decreased markedly. High temperature and prolonged heating also resulted in the loss of ACE inhibitory activity, the loss of free amino groups, and the darker coloration of bovine casein-derived peptides. However, ACE inhibitory peptides, within a concentration range of from 0.01 to 0.2 mg/ml, showed no cytotoxicity to Caco-2 and ECV-304 cell lines after heat treatment. This indicated that high temperature and alkaline heat treatment impaired the stability of bovine casein-derived ACE inhibitory peptides.

Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6.

AIM: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro. METHODS: HSCs were derived from the livers of adult male Sprague-Dawley rats. IL-6 expression was evaluated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting. RESULTS: IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P < 0.01). Moreover, Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P < 0.01). Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.

[Preparation and identification of rabbit antibody against LRR of Nogo-66 receptor (NgR)].

AIM: To prepare rabbit antibody against LRR of Nogo-66 receptor (NgR) and identify its properties. METHODS: LRR protein was expressed in E.coli BL21. Rabbits were immunized with purified LRR protein to prepare anti-LRR antibody. The titer and specificity of prepared antibodies were identified by Western blot and immunohistochemical staining, respectively. RESULTS: Purified rabbit anti-rat LRR antibody with high titer was obtained. The anti-LRR Ab showed good specificity and could be used to detect the NgR in rat brain and spinal cord tissues. Immunohistochemical staining indicated that NgR was expressed widely in spinal cord neurons. CONCLUSION: Successful preparation of anti-rat LRR antibody provides a useful tool for identification and further functional study of NgR molecule.

Expression and localization of p80 interleukin-1 receptor protein in the rat spinal cord.

The biological effects of interleukin (IL)-1 are mediated by two distinct receptors, the p80 or type I (IL-1RI) and p68 or type II (IL-1RII) receptors. Because IL-1RII has a short, 29-amino acid cytoplasmic domain which may not be sufficient for signaling, there is considerable evidence indicating that IL-1 may signal exclusively through the IL-1RI receptor. Here, we report the expression, distribution, and cellular localization of the IL-1RI protein in the adult rat spinal cord in vivo and embryonic spinal cord in vitro. We found that IL-1RI was expressed in both the gray and white matter throughout the entire length of the spinal cord and was localized in neurons of the anterior horn, astrocytes, oligodendrocytes, and central canal ependymal cells. Interestingly, resting microglia were negative for IL-1RI. In primary cultures obtained from the embryonic day (E) 15 rats, IL-1RI was expressed in neurons, astrocytes, and oligodendrocytes as well as microglia. These data provide both in vivo and in vitro evidence that neurons and glial cells express the IL-1RI proteins. The differential expression of IL-1RI in the developing, but not mature, microglia may indicate the difference of these cells in response to IL-1 stimuli during maturation. The distribution and cellular localization of IL-1RI proteins in the spinal cord provide a molecular basis for understanding the reciprocal interaction between the immune and the central nervous systems.

Upregulation of type I interleukin-1 receptor after traumatic spinal cord injury in adult rats.

Post-traumatic inflammation response has been implicated in secondary injury mechanisms after spinal cord injury (SCI). Interleukin-1 (IL-1) is a key inflammatory mediator that is increasingly expressed after SCI. The action of IL-1 is mediated through its functional receptor, type I interleukin-1 receptor (IL-1RI). However, whether this receptor is expressed after SCI remains to be elucidated. In the present study, the temporospatial expression of IL-1RI was detected in rats that received a moderate contusive SCI (a 10 g rod dropped at a height of 12.5 mm) at the ninth to tenth thoracic vertebral level using a widely used New York University impact device. Our study demonstrated that IL-1RI was slightly increased at 4 h post-injury compared to the normal or sham-operated controls, reached the peak at 8 h at mRNA level (4.44-fold, P<0.01) and 1 d at protein level (2.62-fold, P<0.01). IL-1RI remained at its elevated levels for a relatively long duration (4 h-7 days). Spatially, IL-1RI was observed throughout the entire length of a 10 mm-long cord segment containing the injury epicenter. Colocalization of IL-1RI was found in neurons, oligodendrocytes, astrocytes, and activated microglia. Our results suggest that the elevated expression of IL-1RI after SCI may contribute to posttraumatic inflammation responses of IL-1.