3D skin bioprinting as promising therapeutic strategy for radiation-associated skin injuries.

Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.

Phosphate Metabolic Inhibition Contributes to Irradiation-Induced Myelosuppression through Dampening Hematopoietic Stem Cell Survival.

Myelosuppression is a common and intractable side effect of cancer therapies including radiotherapy and chemotherapy, while the underlying mechanism remains incompletely understood. Here, using a mouse model of radiotherapy-induced myelosuppression, we show that inorganic phosphate (Pi) metabolism is acutely inhibited in hematopoietic stem cells (HSCs) during irradiation-induced myelosuppression, and closely correlated with the severity and prognosis of myelosuppression. Mechanistically, the acute Pi metabolic inhibition in HSCs results from extrinsic Pi loss in the bone marrow niche and the intrinsic transcriptional suppression of soluble carrier family 20 member 1 (SLC20A1)-mediated Pi uptake by p53. Meanwhile, Pi metabolic inhibition blunts irradiation-induced Akt hyperactivation in HSCs, thereby weakening its ability to counteract p53-mediated Pi metabolic inhibition and the apoptosis of HSCs and consequently contributing to myelosuppression progression. Conversely, the modulation of the Pi metabolism in HSCs via a high Pi diet or renal Klotho deficiency protects against irradiation-induced myelosuppression. These findings reveal that Pi metabolism and HSC survival are causally linked by the Akt/p53-SLC20A1 axis during myelosuppression and provide valuable insights into the pathogenesis and management of myelosuppression.

Neutrophils-derived Spink7 as one safeguard against experimental murine colitis.

The uncontrolled abnormal intestinal immune responses play important role in eliciting inflammatory bowel disease (IBD), yet the molecular events regulating intestinal inflammation during IBD remain poorly understood. Here, we describe an endogenous, homeostatic pattern that controls inflammatory responses in experimental murine colitis. We show that Spink7 (serine peptidase inhibitor, kazal type 7), the ortholog of human SPINK7, is significantly upregulated in dextran sodium sulfate (DSS)-induced murine colitis model. Spink7-deficient mice showed highly susceptible to experimental colitis characterized by enhanced weight loss, shorter colon length, higher disease activity index and increased colonic tissue destruction. Bone marrow reconstitution experiments demonstrated that expression of Spink7 in the immune compartment makes main contribution to its protective role in colitis. What's more, neutrophils are the primary sources of Spink7 in experimental murine colitis. Loss of Spink7 leads to augmented productions of multiple chemokines and cytokines in colitis. In summary, this study identifies neutrophils-derived endogenous Spink7-mediated control of chemokines/cytokines production as a molecular mechanism contributing to inflammation resolution during colitis.

Chronic oral depleted uranium leads to reproductive damage in male rats through the ROS-hnRNP A2/B1-COX-2 signaling pathway.

Depleted uranium (DU) is widely used in civil and military activities. The testis is one of the target organs of DU chronic toxicity. In this study, male SD rats were chronically exposed to DU by 3, 30, 300 mg U/kg through oral intake. After 6 months and 12 months of exposure, it was found that DU could lead to increased oxidative stress levels, decreased glutathione S-transferases (GSTs) expression, resulting in testicular injury and decreased serum testosterone (T) level in rats. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) expression increases with the increase of DU exposure dose. After upregulation of hnRNP A2/B1 expression, the GC-1 cell injury caused by DU is aggravated, suggesting that hnRNP A2/B1 may play an important role in the reproductive toxicity of DU. At the same time, 12 months after chronic oral exposure to DU, the expression level of cyclooxygenase-2 (COX-2) and proinflammatory factor prostaglandin E2 (PGE2) in testicular tissue were increased, and the level of hnRNP A2/B1 caused by DU was decreased by reactive oxygen scavenger N-acetylcysteine (NAC). As hnRNP A2/B1 is a COX-2 regulator, DU may lead to the upregulation of hnRNP A2/B1 expression through the increase of oxidative stress level in germ cells, which in turn leads to the increase of COX-2 and PGE2 level, and ultimately result in the reproductive toxicity. In this study, the regulation mechanism of the ROS-hnRNP A2/B1-COX-2 pathway on DU-induced reproductive damage in male rats was hypothesized, providing a new target for the prevention and treatment of chronic poisoning of DU.

Ethylmalonic encephalopathy 1 initiates overactive autophagy in depleted uranium-induced cytotoxicity in the human embryonic kidney 293 cells.

The kidney is the target of the acute toxicity of depleted uranium (DU). However, the mechanism of DU-induced cytotoxicity is not clear. The study was to demonstrate the role of autophagy in DU-induced cytotoxicity and to determine the potential mechanism. We confirmed that after a 4-h exposure to DU, the autophagic vacuoles and the autophagy marker light chain 3-II in the human embryonic kidney 293 cells (HEK293) increased, and cytotoxicity decreased by abrogation of excessive autophagy using autophagy inhibitor. We also found activation of nucleus p53 and inhibiting mTOR pathways in DU-treated HEK293 cells. Meanwhile, ethylmalonic encephalopathy 1 (ETHE1) decreased as the exposure dose of DU increased, with increasing autophagy flux. We suggested that by reducing ETHE1, activation of the p53 pathway, and inhibiting mTOR pathways, DU might induce overactive autophagy, which affected the cytotoxicity. This study will provide a novel therapeutic target for the treatment of DU-induced cytotoxicity.

A review of biological effects and treatments of inhaled depleted uranium aerosol.

Depleted uranium (DU) is primarily used for DU bombs and DU tanks in the military. Aerosol inhalation is considered the primary route of DU exposure. Although laboratory tests have confirmed that inhalation of DU aerosol can cause lung, kidney, and other organ damage, epidemiological studies have found no conclusive evidence that persons in areas with prolonged exposure to DU-containing bombs are affected. After the body inhaled DU aerosols, we first clear the insoluble DU through whole-lung lavage (WLL). Then we eliminate the soluble uranium by the chelating agent. Besides, reducing DU damage to tissues and cells through drugs is also an important treatment method. In future research, emphasis should be placed on the damage mechanism of DU aerosol, the laboratory and clinical research of DU chelating agents, the research on the combination of DU chelating agent and WLL, and the research and development of new drugs to prevent DU damage.

MicroRNA-34a deficiency leads to impaired wound closure by augmented inflammation in mice.

BACKGROUND: Proper inflammation resolution is critical for cutaneous wound healing and disordered inflammation resolution results in chronic nonhealing wounds. However, the cellular and molecular mechanisms for resolution of inflammation during skin wound healing are not well understood. MicroRNA-34a is regarded as one tumor suppressor with complexed immune regulatory effects, yet its role during skin wound repair is still unclear. METHODS: Circular full thickness excisional wounds were made on the dorsal skin of C57 mice and miR-34a expression pattern was examined by real time RT-PCR and in situ hybridization. The wound healing rates and histologic morphometric analysis were quantified and compared between wounds treated with antagomir-34a and autologous control antagomir-NC wounds, as well as wounds between miR-34a knockout (KO) and wild type (WT) mice. Immunohistochemistry (IHC) for both MPO and F4/80 were performed to examine the infiltrative neutrophils and macrophages in wounds from miR-34a KO and WT mice. Cytokines including IL-1ß, IL-6, TNF-α and IL-10, were detected and analyzed by real time RT-PCR during wound healing. IHC for IL-6 and p-STAT3 were quantified, and WB for p-STAT3 and IL-6R were examined in wounds of miR-34a KO and WT mice. RESULTS: We found miR-34a was significantly downregulated in the inflammatory phase and back to normal levels in the proliferative phase. Both topical knockdown wounds miR-34a levels by antagomir gel and systematic knockout miR-34a using KO mice resulted in impaired wound healing with delayed re-epithelialization and augmented inflammation. IHC results indicated that there were more residual infiltrative inflammatory cells in the proliferative phase. Moreover, over-activated IL-6/STAT3 signal pathway was identified in the wounds of miR-34a KO mice. CONCLUSIONS: Our findings reveal that miR-34a deficiency augments skin wound inflammation response and leads to impaired wound healing, which suggest that targeted inhibition of miR-34a for tissue repair/regeneration should be with serious consideration.

dTMP-GH Fusion Protein Therapy Improves Survival after Radiation Injury Combined with Skin-Burn Trauma in Mice.

Exposure to ionizing radiation combined with traumatic tissue injury is an important life-threatening condition found in the civilian populations after nuclear and radiological events. The significance feature of radiation combined injury (RCI) is the severe combined effect, which makes the injury more complicated. At present, there are limited measures available to treat RCI. Here we show that a chimeric protein dTMP-GH, fusing human growth hormone (hGH) with a tandem dimer of thrombopoietin mimetic peptide (dTMP), could be an effective therapy agent for RCI in a mice model. In this study, using a RCI mouse model exposed to 60Co γ-ray photons (6.0 Gy, 0.3 Gy/min) followed by a 20% total-body-surface-area burns (henceforth called: RB-CI) was established. Administration of dTMP-GH (200 ug/kg) for 10 consecutive days beginning at 24 h after injury improved survival rate during a 30-day observation period compared with the control vehicle group. dTMP-GH treatment also showed enhanced bone marrow hematopoiesis recovery determined by peripheral blood analysis and bone marrow histopathology. Meanwhile, dTMP-GH treatment accelerated skin wound closure and mitigated ileum injury in the RCI model. These results suggest that dTMP-GH may prove to be an effective therapeutic drug for RCI.

MiR-21 ameliorates age-associated skin wound healing defects in mice.

BACKGROUND: The cellular and molecular mechanisms responsible for the age-associated delay of cutaneous wound healing are still not well understood. Previous studies have shown that miR-21 plays key roles during skin wound healing. We presumed that dysregulation of miR-21 may be involved in age-associated defects in wound healing and that miR-21 may be one potential therapeutic target by which to ameliorate wound defects in elderly subjects. METHODS: Circular full thickness excisional wounds were made on the dorsal skin of young (2-month-old) and aged (12-month-old) female mice. The wound healing rates were quantified and compared between wild-type and miR-21 knock-in mice. Both histologic and morphometric analyses of the wounds were evaluated. Furthermore, the expression patterns of miR-21 during wound healing in both young and aged mice were assessed by in situ hybridization. The effects of topical miR-21 overexpression on wound healing in aged mice were estimated by both wound closure quantification and histological analyses. RESULTS: Aged miR-21 knock-in female mice showed significantly improved wound healing compared to their wild-type counterparts with respect to mature granulation tissue, smaller wound width and thinner epidermis. The expression patterns of miR-21 showed that miR-21 levels were insufficient for repairing granulation tissue in aged mice. Intradermal injection of miR-21 plasmid around wounds could upregulate miR-21 levels during wound healing and ameliorate age-associated skin wound defects. CONCLUSIONS: The results of the present study reveal that the upregulation of miR-21 levels could improve wound repair in aged mice, which suggests that a therapeutic strategy targeting miR-21 expression in age-associated wound healing may be feasible.

Identification of G2/M phase transition by sequential nuclear and cytoplasmic changes and molecular markers in mice intestinal epithelial cells.

Although the regulatory network of G2/M phase transition has been intensively studied in mammalian cell lines, the identification of morphological and molecular markers to identify G2/M phase transition in vivo remains elusive. In this study, we found no obvious morphological changes between the S phase and G2 phase in mice intestinal epithelial cells. The G2 phase could be identified by Brdu incorporation resistance, marginal and scattered foci of histone H3 phosphorylated at Ser10 (pHH3), and relatively intact Golgi ribbon. Prophase starts with nuclear transformation in situ, which was identified by a series of prophase markers including nuclear translocation of cyclinB1, fragmentation of the Golgi complex, and a significant increase in pHH3. The nucleus started to move upwards in the late prophase and finally rounded up at the apical surface. Then, metaphase was initiated as the level of pHH3 peaked. During anaphase and telophase, pHH3 sharply decreased, while Ki67 was obviously bound to chromosomes, and PCNA was distributed throughout the whole cell. Based on the aforementioned markers and Brdu pulse labeling, it was estimated to take about one hour for most crypt cells to go through the G2 phase and about two hours to go through the G2-M phase. It took much longer for crypt base columnar (CBC) stem cells to undergo G2-prophase than rapid transit amplifying cells. In summary, a series of sequentially presenting markers could be used to indicate the progress of G2/M events in intestinal epithelial cells and other epithelial systems in vivo.

Development of a sandwich enzyme-linked immunosorbent assay for dTMP-GH fusion protein by rational immunogen selection.

dTMP-GH is a chimeric protein containing a tandem dimer of thrombopoietin mimetic peptide (dTMP) fused to human growth hormone (hGH) prepared previously by our team. It shows significant bioactivity in promoting thrombocytopoiesis, but detection of intact dTMP-GH in plasma is still a challenge due to the presence of endogenous hGH. In this study, a rabbit polyclonal antibody with high affinity to dTMP was obtained with a BSA-conjugated immunogen composed of 20 amino acids sequence spanning two TMP and the linker. A monoclonal antibody termed as 3B2 was screened out by using immunizing mice with whole dTMP-GH, which was proved to simultaneously interact with rhGH, TMP-GH, and dTMP-GH, respectively. In this study, we developed a specific and sensitive sandwich enzyme-linked immunosorbent assay (ELISA) with two antibodies (one polyclonal and one HRP-conjugated monoclonal) to quantify dTMP-GH. The polyclonal antibody and HRP-conjugated monoclonal antibody 3B2 were applied as the capture antibody and detection antibody, respectively. A good correlation between ELISA and bicinchoninic acid (BCA) assay in the quantification of diluted dTMP-GH was observed (r2 = 0.996). Meanwhile, the standard curve of this ELISA method was found in a linear relationship between 0.2 and 10 ng/mL in the presence of rabbit plasma. In vivo experiments demonstrate that the newly developed method is effective to detect dTMP-GH in rabbits, which paves the way for further pharmacokinetic evaluation.

Effect of radiation-induced endothelial cell injury on platelet regeneration by megakaryocytes.

Thrombocytopenia is an important cause of hemorrhage and death after radiation injury, but the pathogenesis of radiation-induced thrombocytopenia has not been fully characterized. Here, we investigated the influence of radiation-induced endothelial cell injury on platelet regeneration. We found that human umbilical vein endothelial cells (HUVECs) underwent a high rate of apoptosis, accompanied by a significant reduction in the expression of vascular endothelial growth factor (VEGF) at 96 h after radiation. Subsequent investigations revealed that radiation injury lowered the ability of HUVECs to attract migrating megakaryocytes (MKs). Moreover, the adhesion of MKs to HUVECs was markedly reduced when HUVECs were exposed to radiation, accompanied by a decreased production of platelets by MKs. In vivo study showed that VEGF treatment significantly promoted the migration of MKs into the vascular niche and accelerated platelet recovery in irradiated mice. Our studies demonstrate that endothelial cell injury contributes to the slow recovery of platelets after radiation, which provides a deeper insight into the pathogenesis of thrombocytopenia induced by radiation.

Regulation of Embryonic Stem Cell Self-Renewal and Differentiation by MicroRNAs.

MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. They play an important role in various cellular processes such as apoptosis, differentiation, secretion, and proliferation. Embryonic stem cells (ESCs) are derived from the inner cell mass of the blastocyst stage of the embryo. miRNAs are critical factors for the self-renewal and differentiation of ESCs. In this review, we will focus on the role of miRNAs in the self-renewal and directional differentiation of ESCs. We will present the current knowledge on key points related to miRNA biogenesis and their function in ESCs.

Single step synthesis of amine-functionalized mesoporous magnetite nanoparticles and their application for copper ions removal from aqueous solution.

Amine-functionalized mesoporous superparamagnetic Fe3O4 nanoparticles with an average size of 70nm have been synthesized using a single step solvothermal method by the introduction of triethylenetetramine (TETA), a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. The synthesized nanoparticles were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, nitrogen adsorption/desorption isotherm, vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). It is confirmed that the magnetic nanoparticles have been functionalized with TETA during the synthetic process, and the concentration of TETA is crucial for the formation of monodisperse mesoporous nanoparticles. The obtained single-crystal magnetic nanoparticles have a high magnetization, which enhances their response to external magnetic field and therefore should greatly facilitate the manipulation of the particles in practical uses. Reaction parameters affecting the formation of mesoporous structure were explored, and a possible formation mechanism involving templated aggregation and recrystallization processes was proposed. The capacity of the synthesized amine-functionalized Fe3O4 nanoparticles toward Cu(II) removal from aqueous solution was investigated. The adsorption rate of Cu(II) on amine-functionalized Fe3O4 nanoparticles followed a pseudo-second order kinetic model. The results of this study demonstrated that the amine-functionalized mesoporous superparamagnetic Fe3O4 nanoparticles could be used as an efficient adsorbent in water treatment and would also find potential application for Cu(II) removal in vivo.

Calcium Influx of Mast Cells Is Inhibited by Aptamers Targeting the First Extracellular Domain of Orai1.

Using the systematic evolution of ligands by exponential enrichment (SELEX) method, we identified oligonucleotides that bind to the first extracellular domain of the Orai1 protein with high affinities and high specificities. These ligands were isolated from a random single-strand DNA (ssDNA) library with 40 randomized sequence positions, using synthesized peptides with amino acid sequences identical to the first extracellular domain of the Orai1 protein as the targets for SELEX selection. Seven aptamers were obtained after 12 rounds of SELEX. An enzyme-linked oligonucleotide assay (ELONA) was performed to determine the affinities of the aptamers. Aptamer Y1 had the highest affinity (Kd = 1.72×10-8 mol/L) and was selected for functional experiments in mast cells. Using LAD2 cells with the human high-affinity IgE receptor and Ca2+ release activation channel (CRAC), we demonstrated that Aptamer Y1 blocked IgE-mediated ß-hexosaminidase release from cells triggered by biotin-IgE and streptavidin. A specific binding assay showed that Aptamer Y1 not only bound the Orai1 peptide specifically but also that the Orai1 peptide did not bind significantly to other random oligonucleotide molecules. Furthermore, Aptamer Y1 regulation of intracellular Ca2+ mobilization was investigated by probing intracellular Ca2+ with a Fluo-4-AM fluorescent probe. We found that Aptamer Y1 inhibits Ca2+ influx into antigen-activated mast cells. These results indicate that the target of Aptamer Y1 in the degranulation pathway is upstream of Ca2+ influx. Therefore, these oligonucleotide agents represent a novel class of CRAC inhibitors that may be useful in the fight against allergic diseases.

Downregulation of miR-205 in migrating epithelial tongue facilitates skin wound re-epithelialization by derepressing ITGA5.

Keratinocyte migration is essential for re-epithelialization during skin wound healing, but the molecular mechanisms regulating this cellular response remain to be completely clarified. Here we show that keratinocyte-specific miR-205 is significantly downregulated in the leading edge of the migrating epithelial tongue after skin injury in mice. In HaCaT keratinocytes, miR-205 could be downregulated by TGF-ß1 stimulation. And similar to the effect of TGF-ß1, miR-205 knockdown could promote keratinocyte migration in wound scratch model in vitro. Furthermore, topical inhibition of miR-205 by administrating Pluronic gel containing antagomir-205 could accelerate re-epithelialization in mouse skin wound model in vivo. Moreover, we identified integrin alpha 5 (ITGA5) as one key functional miR-205 target in the re-epithelialization process and epidermal downregulation of miR-205 may desilence ITGA5 to promote keratinocyte migration. And knockdown of ITGA5 would abolish the pro-migratory effects of miR-205 inhibition in vitro. What's more, we found dysregulation of miR-205 and its target ITGA5 in epidermis of clinical chronic wound samples with persistence of high level miR-205 and absence of ITGA5. Our findings indicate that downregulation of miR-205 in the leading migrating keratinocytes is critical for re-epithelialization and miR-205 may be a potential therapeutic target for chronic wounds.

Cell Density-Dependent Upregulation of PDCD4 in Keratinocytes and Its Implications for Epidermal Homeostasis and Repair.

Programmed cell death 4 (PDCD4) is one multi-functional tumor suppressor inhibiting neoplastic transformation and tumor invasion. The role of PDCD4 in tumorigenesis has attracted more attention and has been systematically elucidated in cutaneous tumors. However, the normal biological function of PDCD4 in skin is still unclear. In this study, for the first time, we find that tumor suppressor PDCD4 is uniquely induced in a cell density-dependent manner in keratinocytes. To determine the potential role of PDCD4 in keratinocyte cell biology, we show that knockdown of PDCD4 by siRNAs can promote cell proliferation in lower cell density and partially impair contact inhibition in confluent HaCaT cells, indicating that PDCD4 serves as an important regulator of keratinocytes proliferation and contact inhibition in vitro. Further, knockdown of PDCD4 can induce upregulation of cyclin D1, one key regulator of the cell cycle. Furthermore, the expression patterns of PDCD4 in normal skin, different hair cycles and the process of wound healing are described in detail in vivo, which suggest a steady-state regulatory role of PDCD4 in epidermal homeostasis and wound healing. These findings provide a novel molecular mechanism for keratinocytes' biology and indicate that PDCD4 plays a role in epidermal homeostasis.

Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study.

Fatigue and diarrhea are the most frequent adverse effects of pelvic radiotherapy, while their etiologies are largely unknown. The aim of this study is to investigate the correlations between fatigue, diarrhea, and alterations in gut microbiota induced by pelvic radiotherapy. During the 5-week treatment of pelvic radiotherapy in 11 cancer patients, the general fatigue score significantly increased and was more prominent in the patients with diarrhea. The fatigue score was closely correlated with the decrease of serum citrulline (an indicator of the functional enterocyte mass) and the increases of systemic inflammatory proteins, including haptoglobin, orosomuoid, α1-antitrypsin and TNF-α. Serum level of lipopolysaccharide (LPS) was also elevated, especially in the patients with diarrhea indicating epithelial barrier breach and endotoxemia. Pyrosequencing analysis of 16S rRNA gene revealed that microbial diversity, richness, and the Firmicutes/Bacteroidetes ratio were significantly altered prior to radiotherapy in patients who later developed diarrhea. Pelvic radiotherapy induced further changes in fecal microbial ecology, some of which were specific to the patients with or without diarrhea. Our results indicate that gut microbial dysbiosis prior to radiation therapy may be exploited to predict development of diarrhea and to guide preventive treatment options. Radiation-induced dysbiosis may contribute to pelvic radiation disease, including mucositis, diarrhea, systemic inflammatory response, and pelvic radiotherapy-associated fatigue in cancer patients.

Hyperplasia of pericytes is one of the main characteristics of microvascular architecture in malignant glioma.

OBJECTIVES: To investigate the role of pericytes in constructing the malformed microvessels (MVs) and participating microvascular architecture heterogeneity of glioma. METHODS: Forty human glioma tissue samples (WHO grade II-IV) were included in present study. Observation of blood vessel patterns, quantitative analysis of endothelial cells (ECs)- and pericyte-labeled MVs and comparison between malignant grades based on single- or double-immunohistochemical staining. The MV number density (MVND), microvascular pericyte number density (MPND), and microvascular pericyte area density (MPAD) were calculated. The expression of PDGFß was also scored after immunostaining. RESULTS: In grade II glioma, most of tumor MVs were the thin-wall CD34+ vessels with near normal morphology. In addition to thin-wall CD34+ MVs, more thick-wall MVs were found in grade III glioma, which often showed α-SMA positive. Most of MVs in grade IV glioma were in the form of plexus, curled cell cords and glomeruloid microvascular proliferation while the α-SMA+ cells were the main components. The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression. With the increase of glioma grades, the α-SMA+ MVND, CD34+ MVND and MPND were significantly augmented although the increase of CD34+ MVND but not MPAD was statistically insignificant between grade III and IV. It was interesting that some vessel-like structures only consist of α-SMA+ cells, assuming the guiding role of pericytes in angiogenesis. The expression level of PDGFß was upregulated and directly correlated with the MPND in different glioma grades. CONCLUSION: Hyperplasia of pericytes was one of the significant characteristics of malignant glioma and locally proliferated pericytes were the main constituent of MVs in high grade glioma. The pathological characteristics of pericytes could be used as indexes of malignant grades of glioma.

P68 RNA helicase as a molecular target for cancer therapy.

The DEAD-box family of RNA helicase is known to be required in virtually all cellular processes involving RNA, and p68 is a prototypic one of the family. Reports have indicated that in addition to ATPase and RNA helicase ability, p68 can also function as a co-activator for transcription factors such as estrogen receptor alpha, tumor suppressor p53 and beta-catenin. More than that, post-translational modification of p68 including phosphorylation, acetylation, sumoylation, and ubiquitylation can regulate the coactivation effect. Furthermore, aberrant expression of p68 in cancers highlights that p68 plays an important role for tumorgenesis and development. In this review, we briefly introduce the function and modulation of p68 in cancer cells, and put forward envisagement about future study about p68.