Vaccinia viral A26 protein is a fusion suppressor of mature virus and triggers membrane fusion through conformational change at low pH.

Vaccinia mature virus requires A26 envelope protein to mediate acid-dependent endocytosis into HeLa cells in which we hypothesized that A26 protein functions as an acid-sensitive membrane fusion suppressor. Here, we provide evidence showing that N-terminal domain (aa1-75) of A26 protein is an acid-sensitive region that regulates membrane fusion. Crystal structure of A26 protein revealed that His48 and His53 are in close contact with Lys47, Arg57, His314 and Arg312, suggesting that at low pH these His-cation pairs could initiate conformational changes through protonation of His48 and His53 and subsequent electrostatic repulsion.

Interleukin-37 is highly expressed in regulatory T cells of melanoma patients and enhanced by melanoma cell secretome.

Immune suppression is one of the 10 hallmarks of cancer. Interleukin-37 (IL-37), a member of the IL-1 family, inhibits both innate and adaptive immunity, and has been shown to modulate immune responses in various disease conditions. Yet, IL-37 has rarely been investigated in cancer patients, and its biological role in cancer remains to be elucidated.

CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma.

: Cancers are composed of heterogeneous subpopulations with various tumor-initiating capacities, yet key stem cell genes associated with enhanced tumor-initiating capacities and their regulatory mechanisms remain elusive. Here, we analyzed patient-derived xenografts from melanoma, colon, and pancreatic cancer tissues and identified enrichment of tumor-initiating cells in MHC class I-hi cells, where CDK1, a master regulator of the cell cycle, was upregulated. Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells increased their spheroid forming ability, tumorigenic potential, and tumor-initiating capacity; inhibition of CDK1 with pharmacologic agents reduced these characteristics, which was unexplained by the role of CDK1 in regulating the cell cycle.

Downregulation of CITED2 contributes to TGFβ-mediated senescence of tendon-derived stem cells.

Tendon-derived stem cells (TDSCs) are multipotent adult stem cells with potential applications in tendon and tendon-bone junction repair. However, cellular characteristics change during in vitro passaging. Therefore, elucidation of the molecular and cellular mechanisms of tendon aging will be essential for the development of TDSC-based therapies.

Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.

Major limitations of current melanoma treatments are for instances of relapse and the lack of therapeutic options for BRAF wild-type patients who do not respond to immunotherapy. Many studies therefore focus on killing resistant subpopulations, such as Melanoma Initiating Cells (MICs) to prevent relapse. Here we examined whether combining a GSI (γ-Secretase Inhibitor) with ABT-737 (a small molecule BCL-2/BCL-XL/BCL-W inhibitor) can kill both the non-MICs (bulk of melanoma) and MICs.

Use of a MCL-1 inhibitor alone to de-bulk melanoma and in combination to kill melanoma initiating cells.

MCL-1 (BCL-2 family anti-apoptotic protein) is responsible for melanoma's resistance to therapy. Cancer initiating cells also contribute to resistance and relapse from treatments. Here we examined the effects of the MCL-1 inhibitor SC-2001 in killing non melanoma-initiating-cells (bulk of melanoma), and melanoma-initiating-cells (MICs).

Understanding melanoma stem cells.

Tumors are incredibly diverse and contain many different subpopulations of cells. The cancer stem cell (CSC) subpopulation is responsible for many aspects of tumorigenesis and has been shown to play an important role in melanoma development, progression, drug resistance and metastasis. However, it is becoming clear that tumor cell populations are dynamic and can be influenced by many factors, such as signals from the tumor microenvironment and somatic evolution.

Efficacy of tripterygium glycosides tablet in treating ankylosing spondylitis: a systematic review and meta-analysis of randomized controlled trials.

Hundreds of randomized controlled trials (RCTs) on tripterygium glycosides tablet (TGT) in the treatment of ankylosing spondylitis (AS) have been published, but the therapeutic effects have never been systematically reviewed yet. The aim of this meta-analysis was to evaluate the efficacy of TGT on AS based on RCTs. PubMed, ScienceDirect, Cochrane Library, China Journals Full-text Database, and Wanfang Data were searched.

Extracellular forms of IL-37 inhibit innate inflammation in vitro and in vivo but require the IL-1 family decoy receptor IL-1R8.

Similar to IL-1α and IL-33, IL-1 family member IL-37b translocates to the nucleus and is associated with suppression of innate and adaptive immunity. Here we demonstrate an extracellular function of the IL-37 precursor and a processed form. Recombinant IL-37 precursor reduced LPS-induced IL-6 by 50% (P < 0.

Combining a BCL2 inhibitor with the retinoid derivative fenretinide targets melanoma cells including melanoma initiating cells.

Investigations from multiple laboratories support the existence of melanoma initiating cells (MICs) that potentially contribute to melanoma's drug resistance. ABT-737, a small molecule BCL-2/BCL-XL/BCL-W inhibitor, is promising in cancer treatments, but not very effective against melanoma, with the antiapoptotic protein MCL-1 as the main contributor to resistance. The synthetic retinoid fenretinide N-(4-hydroxyphenyl)retinamide (4-HPR) has shown promise for treating breast cancers.

Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells.

IL-1 family member IL-37 limits innate inflammation in models of colitis and LPS-induced shock, but a role in adaptive immunity remains unknown. Here, we studied mice expressing human IL-37b isoform (IL-37tg) subjected to skin contact hypersensitivity (CHS) to dinitrofluorobenzene. CHS challenge to the hapten was significantly decreased in IL-37tg mice compared with wild-type (WT) mice (-61%; P < 0.

Crystallization and X-ray diffraction of virus-like particles from a piscine betanodavirus.

Dragon grouper nervous necrosis virus (DGNNV), a member of the genus Betanodavirus, causes high mortality of larvae and juveniles of the grouper fish Epinephelus lanceolatus. Currently, there is no reported crystal structure of a fish nodavirus. The DGNNV virion capsid is derived from a single open reading frame that encodes a 338-amino-acid protein of approximately 37 kDa.

MiR397b regulates both lignin content and seed number in Arabidopsis via modulating a laccase involved in lignin biosynthesis.

Plant laccase (LAC) enzymes belong to the blue copper oxidase family and polymerize monolignols into lignin. Recent studies have established the involvement of microRNAs in this process; however, physiological functions and regulation of plant laccases remain poorly understood. Here, we show that a laccase gene, LAC4, regulated by a microRNA, miR397b, controls both lignin biosynthesis and seed yield in Arabidopsis.

Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A.

Chondrosarcoma is a malignant cartilage-forming cancer composed of cells derived from transformed cells that produce cartilage. Conventional chemotherapy and radiotherapy have very limited efficacy in patients with advanced chondrosarcoma. In the present study, we reported a novel therapeutic approach in the treatment of chondrosarcoma cells.

Isolation of human melanoma stem cells using ALDH as a marker.

This unit describes a protocol for establishing a patient-derived tumor xenograft model (PDTX model) of human melanoma and isolating human melanoma stem cells from human melanoma specimens using aldehyde dehydrogenase (ALDH) as a marker. One major limitation of analyzing a small fraction of cancer stem cells from patient tumor samples is that substantial quantities of fresh tumor tissues are not available. To overcome this challenge, we have established a PDTX model of human melanoma.

[Surgical treatment of thoracolumbar burst fractures through Wiltse paraspinal approach].

Objective: To investigate clinical effects and advantages of Wiltse paraspinal approach to thoracolumbar burst fractures.

Methods: From June 2008 to June 2010, the data of 53 patients with thoracolumbar burst fractures with no obviously nerve injury were retrospectively analyzed, including 43 males and 10 females with an average age of 41 years ( ranged, 19 to 62 years). For segmental distribution, 6 cases were T11, 11 cases were T12, 22 cases were L1 and 14 cases were L2.

[Clinical study on treatment of posterolateral fracture of tibial plateau via superior fibular head approach].

Objective: To observe the effectiveness of the superior fibular head approach for the treatment of posterolateral fracture of the tibial plateau.

Methods: Between June 2010 and February 2012, 20 cases of posterolateral fracture of the tibial plateau were treated through superior fibular head approach, including 1 case of simple posterolateral fracture of the tibial plateau and 19 cases of posterolateral fracture of the tibial plateau with other fractures. There were 12 males and 8 females with an average age of 42.

ABT-737 synergizes with Bortezomib to kill melanoma cells.

The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L), and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib) in vitro and in vivo, and further evaluated the mechanisms of action.

[Effectiveness comparison of operative and non-operative treatment for complex proximal humeral fractures in elderly patients].

Objective: To compare the effectiveness between operative and non-operative treatment for 3- and 4-part proximal humeral fractures in elderly patients.

Methods: Between January 2009 and January 2011, 35 patients with 3- or 4-part proximal humeral fractures were treated with open reduction and locking plate internal fixation (n = 20, operative group) and with closed reduction and splint or cast fixation (n = 15, non-operative group). There was no significant difference in gender, age, etiology, fracture type, and disease duration between 2 groups (P > 0.

Dual role of apoptosis-associated speck-like protein containing a CARD (ASC) in tumorigenesis of human melanoma.

Apoptosis-associated Speck-like protein containing a CARD (caspase recruitment domain) (ASC) was originally named because it triggered apoptosis in certain tumors. More recently, however, ASC was found to be a central adaptor protein of inflammasome, which mediates the secretion of protumorigenic inflammation. Here we examined the role of ASC in tumorigenesis of human melanoma.

ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets.

Although the concept of cancer stem cells (CSCs) is well-accepted for many tumors, the existence of such cells in human melanoma has been the subject of debate. In this study, we demonstrate the existence of human melanoma cells that fulfill the criteria for CSCs (self-renewal and differentiation) by serially xenotransplanting cells into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. These cells possess high aldehyde dehydrogenase (ALDH) activity with ALDH1A1 and ALDH1A3 being the predominant ALDH isozymes.

Side population cells from human melanoma tumors reveal diverse mechanisms for chemoresistance.

Side population (SP) cells are identified as cells capable of excluding the fluorescent Hoechst dye and anticancer drugs, and it represents hematopoietic stem cells and chemoresistant cells from several solid tumors. In this study, we confirmed the presence of SP cells in tumors from melanoma patients. Melanoma SP cells overexpressed ATP-binding-cassette (ABC) transporters, ABCB1 and ABCB5.

[Arthroscopic minimally invasive treatment of tibial intercondylar eminence fractures in children].

Objective: To analyze the characteristics of children tibial intercondylar eminence fractures, and introduce arthroscopic minimally invasive techniques for the treatment of tibial intercondylar eminence fractures in children.

Methods: From January 2004 to December 2008, 12 children with tibial intercondylar eminence fractures were treated with cross Kirschner wire fixation after arthroscopic reduction. According to Meyers-McKeever classification systems, there were 1 case of type I, 4 cases of type II, and 7 cases of type III.

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion.

Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.