Tripartite-motif 3 represses ovarian cancer progression by downregulating lactate dehydrogenase A and inhibiting AKT signaling.

The E3 ubiquitin ligase Tripartite-motif 3 (TRIM3) is known to play a crucial role in tumor suppression in various tumors through different mechanisms. However, its function and mechanism in ovarian cancer have yet to be elucidated. Our study aims to investigate the expression of TRIM3 in ovarian cancer and evaluate its role in the development of the disease. Our findings revealed a significant decrease in TRIM3 mRNA and protein levels in ovarian cancer tissues and cells when compared to normal ovarian epithelial tissues and cells. Furthermore, we observed a negative correlation between the protein level of TRIM3 and the FIGO stage, as well as a positive correlation with the survival of ovarian cancer patients. Using gain and loss of function experiments, we demonstrated that TRIM3 can inhibit cell proliferation, migration and invasion of the ovarian cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistic studies showed that TRIM3 interacts with lactate dehydrogenase A, a key enzyme in the glycolytic pathway, through its B-box and coiled-coil domains and induces its ubiquitination and proteasomal degradation, leading to the inhibition of glycolytic ability in ovarian cancer cells. RNA-sequencing analysis revealed significant alterations in the phosphatidylinositol signaling pathways upon TRIM3 overexpression. Additionally, overexpression of TRIM3 inhibited the phosphorylation of AKT. In conclusion, our study demonstrated that TRIM3 exerts a tumor-suppressive effect in ovarian cancer, at least partially, by downregulating LDHA and inhibiting the AKT signaling pathway, and thus leading to the inhibition of glycolysis and limiting the growth of ovarian cancer cells.

IGF2BP2 promotes ovarian cancer growth and metastasis by upregulating CKAP2L protein expression in an m6 A-dependent manner.

Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m6 A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6 A reader, can enhance mRNA stability and promote translation by recognizing m6 A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m6 A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6 A modification in OC tissues. The m6 A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6 A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6 A-dependent manner.

Reproductive Biology and Distribution of the Blue Shark (Prionace glauca) in the Western Indian Ocean.

Due to the limited biological research on the blue shark in the Indian Ocean, such as the lack of a clear understanding of its reproductive biology and distribution, our study analyzed and evaluated the fork length distribution, sexual maturity length, reproductive capacity, and spatiotemporal distribution of blue sharks based on biological data and capture location information collected in the western Indian Ocean from 2010 to 2020. The objective of this study is to provide reliable biological information important in performing future stock assessments vital for species conservation in this region. A total of 791 male (33-249.5 cm FL) and 803 female (12-349.6 cm FL) blue sharks were collected in the West Indian Ocean. We used the morphology of the sexual organs to ascertain their sexual maturity. Results show that the observed size at 50% sexual maturity of male blue sharks in the West Indian Ocean was 161.4cm FL (192.4 cm TL) for males and 179.3 cm FL (213.9 cm TL) for females based on logistic curve analysis. The average litter size of pregnant blue sharks was 33.7 pups. There were significant differences in the distribution of blue shark individuals with different sexual maturity levels in different quarters (p < 0.05). This study suggests that the area near the equator in the Indian Ocean from October to March of the following year may be the mating ground for blue sharks, while the temperate waters in the Indian Ocean are the nursery ground and parturition ground for pregnant and juvenile throughout the whole year. Therefore, it is recommended to adopt a more scientific and reasonable operational method in these areas.

Current status and outlook of minimally invasive treatment for leiomyomas.

OBJECTIVES: Leiomyomas are benign, highly prevalent gynecologic conditions that can cause abnormal uterine bleeding, pelvic pain, urinary difficulties, and/or bladder or rectal obstruction. With advances in medical technology, women are increasingly interested in treatments that avoid surgery and/or preserve the uterus, which has undoubtedly contributed to the development of minimally invasive approaches. This article reviews the literature and evaluates the effectiveness and safety of minimally invasive approaches for the treatment of leiomyomas and describes the current state of development of minimally invasive treatment modalities for leiomyomas. MATERIAL AND METHODS: Web of Science and PubMed were systematically evaluated using the following keywords: uterine artery embolization, high-intensity focused ultrasound, microwave ablation, radiofrequency ablation, myomectomy, hysterectomy, leiomyomas, fertility. English abstracts relevant to the topic were selected and full-text articles were carefully analyzed. RESULTS: Uterine artery embolization is an effective treatment modality that has been widely validated, and the remaining means each have their distinct advantages in clinical practice, but more practical and comparative studies are needed. Minimally invasive myomectomy and minimally invasive hysterectomy are technically advanced compared to classical open surgery and are widely used due to the completion of practical experience, but a continuous interest in non-invasive minimally invasive treatment modalities is retained. CONCLUSIONS: Minimally invasive treatment modalities for leiomyomas have emerged as an important treatment option when considering patient requirements, and further research and practice are needed to support their development into a mainstream modality for the treatment of leiomyomas.

Effects of Solid Fermentation on Polygonatum cyrtonema Polysaccharides: Isolation, Characterization and Bioactivities.

Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders.

A Case-Control Study of 40 Patients with Piriformis Muscle Syndrome to Evaluate Diagnostic Findings Using Two-Dimensional Ultrasound and Shear Wave Elastography.

BACKGROUND Piriformis muscle syndrome (PMS) is a neuropathy caused by compression of the sciatic nerve by the piriformis muscle. This case-control study included 40 patients with PMS and aimed to evaluate the diagnostic findings using two-dimensional ultrasound and shear wave elastography (SWE), as non-invasive and cost-effective diagnostic methods. MATERIAL AND METHODS In order to evaluate the value of two-dimensional ultrasound diagnosis, a new imaging technique called shear wave elastography (SWE) was used in the screening of PMS, with a total of 40 PMS patients and 40 healthy individuals participating in our study. We analyzed the correlation and area under the curve (AUC) of changes in thickness (mm) and Young's modulus (kpa) of the bilateral piriformis muscle (PM). RESULTS We found that PM thickness and Young's modulus on the lesion sides were significantly higher in PMS patients than in controls (P<0.05). Also, we determined that there was a positive correlation between PM thickness and Young's modulus (r=0.454, P<0.05). Using two-dimensional ultrasonic diagnosis and the SWE technique, a specificity of 95.8% and sensitivity of 78.8% were demonstrated in the clinical diagnosis of PM. CONCLUSIONS Two-dimensional ultrasound with SWE technology has demonstrated its superior sensitivity and specificity in diagnosing PMS in the clinic.

Malignancies in systemic rheumatic diseases: A mini review.

There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated with increased risk of most malignancies in patients with systemic rheumatic diseases.

LncRNA SLC25A21-AS1 increases the chemosensitivity and inhibits the progression of ovarian cancer by upregulating the expression of KCNK4.

Owing to high mortality rate, ovarian cancer seriously threatens women's health. Extensive abdominal metastasis and chemoresistance are the leading causes of ovarian cancer deaths. Through lncRNA sequencing, our previous study identified lncRNA SLC25A21-AS1, which was significantly downregulated in chemoresistant ovarian cancer cells. In this study, we aimed to evaluate the role and mechanism of SLC25A21-AS1 in ovarian cancer. The expression of SLC25A21-AS1 was analyzed by qRT-PCR and online database GEPIA. The biological functions of SLC25A21-AS1 and KCNK4 were analyzed by CCK-8, transwell, and flow cytometry. The specific mechanism was analyzed by RNA-sequencing, RNA binding protein immunoprecipitation, rescue experiments, and bioinformatic analysis. SLC25A21-AS1 was decreased in ovarian cancer tissues and cell lines. Overexpression of SLC25A21-AS1 enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin, and inhibited cell proliferation, invasion, and migration, while SLC25A21-AS1-silencing showed the opposite effect. Potassium channel subfamily K member 4 (KCNK4) was significantly up-regulated upon enforced expression of SLC25A21-AS1. Overexpression of KCNK4 inhibited cell proliferation, invasion, migration ability, and enhanced the sensitivity of ovarian cancer cells to paclitaxel and cisplatin. Meanwhile, KNCK4-overexpression rescued the promotive effect of SLC25A21-AS1-silencing on cell proliferation, invasion and migration. In addition, SLC25A21-AS1 could interact with the transcription factor Enhancer of Zeste Homolog 2 (EZH2), while EZH2 knockdown increased the expression of KCNK4 in some of the ovarian cancer cell lines. SLC25A21-AS1 enhanced the chemosensitivity and inhibited the proliferation, migration, and invasion ability of ovarian cancer cells at least partially by blocking EZH2-mediated silencing of KCNK4.

Target Recognition in SAR Images by Deep Learning with Training Data Augmentation.

Mass production of high-quality synthetic SAR training imagery is essential for boosting the performance of deep-learning (DL)-based SAR automatic target recognition (ATR) algorithms in an open-world environment. To address this problem, we exploit both the widely used Moving and Stationary Target Acquisition and Recognition (MSTAR) SAR dataset and the Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset, which consists of selected samples from the MSTAR dataset and their computer-generated synthetic counterparts. A series of data augmentation experiments are carried out. First, the sparsity of the scattering centers of the targets is exploited for new target pose synthesis. Additionally, training data with various clutter backgrounds are synthesized via clutter transfer, so that the neural networks are better prepared to cope with background changes in the test samples. To effectively augment the synthetic SAR imagery in the SAMPLE dataset, a novel contrast-based data augmentation technique is proposed. To improve the robustness of neural networks against out-of-distribution (OOD) samples, the SAR images of ground military vehicles collected by the self-developed MiniSAR system are used as the training data for the adversarial outlier exposure procedure. Simulation results show that the proposed data augmentation methods are effective in improving both the target classification accuracy and the OOD detection performance. The purpose of this work is to establish the foundation for large-scale, open-field implementation of DL-based SAR-ATR systems, which is not only of great value in the sense of theoretical research, but is also potentially meaningful in the aspect of military application.

Effects of "Shi Ying Zi" powder and osthole on immune and antioxidant function of Eimeria tenella-infected broilers.

"Shi Ying Zi" powder is a traditional Chinese herbal formula for preventing and treating coccidiosis. In our previous studies, it showed anticoccidial effects and exhibited the potential to control Eimeria tenella infection. In this research, we evaluated the antioxidation and immune effect of "Shi Ying Zi" powder and its effective active ingredient osthole on coccidiosis-infected broilers to explore the mechanism of its anticoccidial effect. We analyzed changes in the antioxidant index, the pathological changes in cecum, immune index of serum and composition of cecal flora. The results showed that the use of "Shi Ying Zi" powder and osthole alleviated the pathological changes in the cecum, spleen and bursa of Fabricius, upregulated the spleen and bursal weigh index. "Shi Ying Zi" powder of 10 g/kg effectively rocovered the contents of interleukins and immunoglobulin in serum. Osthole increased the proportion of Firmicutes, Actino-bacteria and Lactobacillus in the cecum. In summary, "Shi Ying Zi" powder and osthole have anticoccidial effects, and they also can active the immunity, antioxidant functions and upregulate the beneficial bacteria population in Eimeria tenella-infected broilers.

Friend and foe: the regulation network of ascites components in ovarian cancer progression.

The tumor microenvironment (TME) and its complex role in cancer progression have been hotspots of cancer research in recent years. Ascites, which occurs frequently in patients with ovarian cancer especially in advanced stages, represents a unique TME. Malignant ascites contains abundant cellular and acellular components that play important roles in tumorigenesis, growth, metastasis, and chemoresistance of ovarian cancer through complex molecular mechanisms and signaling pathways. As a valuable liquid biopsy sample, ascites fluid is also of great significance for the prognostic analysis of ovarian cancer. The components of ovarian cancer ascites are generally considered to comprise tumor-promoting factors; however, in recent years studies have found that ascites also contains tumor-suppressing factors, raising new perspectives on interactions between ascites and tumors. Malignant ascites directly constitutes the ovarian cancer microenvironment, therefore, the study of its components will aid in the development of new therapeutic strategies. This article reviews the current research on tumor-promoting and tumor-suppressing factors and molecular mechanisms of their actions in ovarian cancer-derived ascites and therapeutic strategies targeting ascites, which may provide references for the development of novel therapeutic targets for ovarian cancer in the future.

Plasma circRNA microarray profiling identifies novel circRNA biomarkers for the diagnosis of ovarian cancer.

BACKGROUND: Circular RNA (circRNA), a class of RNA with a covalent closed circular structure that widely existed in serum and plasma, has been considered an ideal liquid biopsy marker in many diseases. In this study, we employed microarray and qRT-PCR to evaluate the potential circulating circRNAs with diagnostic efficacy in ovarian cancer. METHODS: We used microarray to explore the circRNA expression profile in ovarian cancer patients' plasma and quantitative real-time (qRT)-PCR approach to assessing the candidate circRNA's expression. Then the receiver operating characteristic (ROC) curve was employed to analyze the diagnostic values of candidate circRNAs. The diagnostic model circCOMBO was a combination of hsa_circ_0003972 and hsa_circ_0007288 built by binary logistic regression. Then bioinformatic tools were used to predict their potential mechanisms. RESULTS: Hsa_circ_0003972 and hsa_circ_0007288 were downregulated in ovarian cancer patients' plasma, tissues, and cell lines, comparing with the controls. Hsa_circ_0003972 and hsa_circ_0007288 exhibited diagnostic values with the Area Under Curve (AUC) of 0.724 and 0.790, respectively. circCOMBO showed a better diagnostic utility (AUC: 0.781), while the combination of circCOMBO and carbohydrate antigen 125 (CA125) showed the highest diagnostic value (AUC: 0.923). Furthermore, the higher expression level of hsa_circ_0007288 in both plasma and ovarian cancer tissues was associated with lower lymph node metastasis potential in ovarian cancer. CONCLUSIONS: Our results revealed that hsa_circ_0003972 and hsa_circ_0007288 may serve as novel circulating biomarkers for ovarian cancer diagnosis.

Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling.

The lives of patients with ovarian cancer are threatened largely due to metastasis and drug resistance. Endogenous peptides attract increasing attention in oncologic therapeutic area, a few antitumor peptides have been approved by the FDA for clinical use over the past decades. However, only few peptides or peptide-derived drugs with antiovarian cancer effects have been identified. Here we focused on the biological roles and mechanism of a peptide named PDHPS1 in ovarian cancer development. Our results indicated that PDHPS1 reduced the proliferation ability of ovarian cancer cells in vitro and inhibited the ovarian cancer growth in vivo. Peptide pull down and following mass spectrometry, Western blot and qRT-PCR revealed that PDHPS1 could bind to protein phosphatase 2 phosphatase activator (PTPA), an essential activator of protein phosphatase 2A (PP2A), which resulted in increase of phosphorylated YAP, further inactivated YAP, and suppressed the expression of its downstream target genes. Flow cytometry, cell membrane permeability test, and IHC staining study demonstrated that there were no observable side effects of PDHPS1 on normal ovarian epithelium and hepatorenal function. Besides, modification of membrane penetration could improve the physicochemical properties and biological activity of PDHPS1. In conclusion, our study demonstrated that the endogenous peptide PDHPS1 serves as an antitumor peptide to inhibit YAP signaling pathway though interacting with PTPA in ovarian cancer.

Hybrid FSK-PSK Waveform Optimization for Radar Based on Alternating Direction Method of Multiplier (ADMM).

In this paper, a new radar signal modulated with a hybrid of the frequency shift keying (FSK) and the phase shift keying (PSK) signal-i.e., the FSK-PSK signal-is studied. Different phase encoding sequences are used to modulate the sub-pulses to obtain lower sidelobe levels and ensure signal orthogonality. In addition, to counter intra-pulse slice repeater jamming of specific length generated by the enemy jammer, an orthogonal waveform made of sub-pulses of equal length based on the FSK-PSK modulation scheme is designed. The simulation results show that the optimized discrete phase encoding sequence can significantly enhance the orthogonality of the sub-pulse in the FSK-PSK signal and effectively suppress the slice repeater jamming. Two algorithms are proposed: (1) the low sidelobe waveform optimization algorithm based on ADMM (LSW-ADMM); and (2) the anti-slice-repeater-jamming algorithm based on ADMM (ASRJ-ADMM). Both algorithms exhibit fast convergence speed and low computational complexity.

Parameter Estimation for Interrupted Sampling Repeater Jamming Based on ADMM.

By repeatedly sampling, storing, and retransmitting parts of the radar signal, interrupted sampling repeater jamming (ISRJ) based on digital radio frequency memory (DRFM) can produce a train of secondary false targets symmetrical to the main false target, threatening to mislead or deceive the victim radar system. This paper proposes a computationally-effective method to estimating the parameters for ISRJ by resorting to the framework of alternating direction method of multipliers (ADMM). Firstly, the analytical form of pulse compression is derived. Then, for the purpose of estimating the parameters of ISRJ, the original problem is transformed into a nonlinear integer optimization model with respect to a window vector. On this basis, the ADMM is introduced to decompose the nonlinear integer optimization model into a series of sub-problems to estimate the width and number of ISRJ's sample slices. Finally, the numerical simulation results show that, compared with the traditional time-frequency (TF) method, the proposed method exhibits much better performance in accuracy and stability.

The Immunomodulatory Effects of Phellodendri Cortex Polysaccharides on Cyclophosphamide-Induced Immunosuppression in Mice.

Cyclophosphamide is a commonly used anticancer drug, and immunosuppression is one of the most common side effects. How to recover the immunological function is important for cyclophosphamide-treated patients. In the present study, Phellodendri Cortex polysaccharides (CPP) could enhance the proliferation of mouse spleen lymphocytes in vitro. The immunoregulatory function of CPP was then investigated in cyclophosphamide-induced immunosuppressed mice. In CPP-treated groups, mice were orally treated with CPP at doses of 1, 0.5, and 0.25 g/kg bodyweight from 1 to 11 d, respectively. The cyclophosphamide was administrated in CPP and cyclophosphamide groups from 12 to 14 d. In the cyclophosphamide and normal control groups, the mice received equal volume of saline from 1 to 14 d. The results showed that CPP (1 g/kg) could significantly increase the bodyweight of mice, even during cyclophosphamide treatment. The organ coefficients of the spleen and thymus were recovered by CPP treatment. CPP upregulated the contents of cytokines (IL-2, IL-6, IFN-γ, and TNF-α) in serum, which were downregulated by cyclophosphamide. The mRNA levels of these cytokines were also elevated by CPP treatment in the spleen. Cyclophosphamide upregulated the expressions of NF-κB p65, TLR4, and MyD88, suggesting that the NF-κB signaling pathway was activated by cyclophosphamide. After CPP treatment, it was recovered to normal level. These results indicated that CPP alleviated the cyclophosphamide-induced immunosuppression.

Tropism-facilitated delivery of CRISPR/Cas9 system with chimeric antigen receptor-extracellular vesicles against B-cell malignancies.

The CRISPR/Cas9 system is an efficient genome-editing system that has been successfully applied in the field of gene therapy. However, clinical applications of the CRISPR/Cas9 system are limited by the delivery method and safety concerns. Extracellular Vesicles (EVs) can be released from almost every type of cell, and they act as shuttles to convey molecules between cells. Here, we used EVs derived from epithelial cells as a biosafety delivery platform for the CRISPR/Cas9 system and modified the EVs with a chimeric-antigen receptor (CAR) to give them selective tropism to tumors. Compared to normal EVs, CAR-EVs accumulated in cancer tumors rapidly and released the CRISPR/Cas9 system targeting the MYC oncogene efficiently, both in vitro and in vivo. Taken together, the combination of EV and CAR was confirmed to be a novel strategy facilitating the use of natural gene therapy platforms in cancer treatment in this proof-of-concept research.

The Impact of Tyrosine Kinase Inhibitors on Chronic Myeloid Leukemia Stem Cells and the Implication in Discontinuation.

BCR-ABL1 tyrosine kinase inhibitors (TKIs) are selective therapies for patients with chronic myeloid leukemia (CML) and induce deep molecular response (DMR). However, ∼60% of patients relapse after the discontinuation of TKIs. Relapse after discontinuation is likely due the inability of TKIs to eradicate CML stem cells (CML-LSCs). In our previous study, 12 out of 22 patients maintained a stable DMR after TKI withdrawal, and we found that fewer patients who were treated with second-generation TKI relapsed compared with those receiving imatinib. Therefore, we hypothesized that second-generation TKIs and imatinib may have different effects on CML-LSCs, which may affect the clinical outcome after TKI discontinuation. To investigate this, we established a TKI discontinuation model in vitro by treating CML CD34+ cells with imatinib and dasatinib continuously for 72 h and then removing the TKI for 24 h. Colony-forming cell (CFC) assays, apoptosis assessment, and proteomic analysis were then performed. We found that TKI discontinuation resulted in less proliferation and CFC output in dasatinib-treated cells compared with imatinib. However, the dasatinib-treated group exhibited increased apoptosis. In the proteomics analysis, we identified 160 upregulated and 151 downregulated proteins when the two TKI discontinuation groups were compared. Importantly, proteins involved in NAD+ nucleosidase activity, mitochondrial ATP synthesis coupled proton transport, and oxidative phosphorylation were significantly expressed, which were mainly involved in metabolic processes. In conclusion, we demonstrate that imatinib and dasatinib have clear differential effects on CML-LSCs through the regulation of mitochondria oxidative phosphorylation, which may provide a new target for eliminating CML-LSCs in the context of TKI discontinuation.

α-Difluoromethylornithine suppresses inflammatory arthritis by impairing myeloid-derived suppressor cells.

OBJECTIVES: The chemopreventive drug α-difluoromethylornithine (DFMO) has been shown to have an antinociceptive effect on mechanical allodynia in inflammatory arthritis by directly inhibiting ornithine decarboxylase (ODC) and decreasing polyamine production in inflammatory sites. However, little is known about the effect of DFMO on the immune system of inflammatory arthritis. Here, we investigated the effect of DFMO in a well-established collagen-induced arthritis (CIA) mouse model and explored its effect on the immune system. METHODS: The effect of DFMO on the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of CIA mice and their associations with disease severity, tissue inflammation and the levels of proinflammatory T-helper (Th) 17 cells in lymphoid tissues were investigated. The effects of DFMO on disease severity and Th17 cells were compared with those of antibody depletion of MDSCs. The arthritis severity was also evaluated by adoptive transfer of MDSCs derived from DFMO- or dH2O-treated mice. RESULTS: In this study, we showed that both MDSCs and Th17 cells were significantly expanded in CIA mice. Treatment by DFMO at the onset of CIA suppressed the development of arthritis and decreased the frequency of MDSCs and Th17 cells. MDSC depletion by anti-Gr-1 mAb achieved a similar result, while combination treatment of both methods did not achieve a significant difference compared to either of the single treatments. In addition, the adoptive transfer of MDSCs derived from dH2O-treated mice with CIA restored the arthritis severity of CIA in mice treated with anti-Gr-1 mAb, while the transfer of MDSCs from DFMO-treated mice did not have such an effect. CONCLUSIONS: Our results identified DFMO as a potential therapeutic drug for the treatment of inflammatory arthritis.

Tumor Necrosis Factor Receptor Type 1-Associated Death Domain Protein Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.

BACKGROUND: Tumor necrosis factor receptor type 1-associated death domain protein (TRADD) mediates programmed cell death signaling as well as the Fas-induced cell death pathway. The downregulation of TRADD is found to be associated with the occurrence of many cancers. The present study was designed to investigate the association between TRADD and clinicopathologic features as well as its clinical significance in acute myeloid leukemia (AML). METHODS: Real-time polymerase chain reaction was performed in 100 new AML, 23 AML complete remission patients, and 20 normal individuals. All statistical analysis was performed using SPSS software. RESULTS: It was found that the expression of TRADD messenger RNA was lower in new AML patients as compared to healthy individuals and complete remission patients (P = 0.00239). Moreover, TRADD messenger RNA levels were associated with clinical factors such as risk classification (P = 0.0023) and complete remission (P = 0.0147). Kaplan-Meier analysis revealed that the AML patients with high TRADD expression had significantly prolonged overall survival and higher complete remission compared with low TRADD expressing patients. CONCLUSIONS: It is concluded that downregulation of TRADD may be an independent potential prognostic biomarker in AML.