Mammalian reovirus µ1 protein attenuates RIG-I and MDA5-mediated signaling transduction by blocking IRF3 phosphorylation and nuclear translocation.

Mammalian reovirus (MRV) is a non-enveloped, gene segmented double-stranded RNA (dsRNA) virus. It is an important zoonotic pathogen that infects many mammals and vertebrates that act as natural hosts and causes respiratory and digestive tract diseases. Studies have reported that RIG-I and MDA5 in the innate immune cytoplasmic RNA-sensing RIG-like receptor (RLR) signaling pathway can recognize dsRNA from MRV and promote antiviral type I interferon (IFN) responses. However, the mechanism by which many MRV-encoded proteins evade the host innate immune response remains unclear. Here, we show that exogenous µ1 protein promoted the proliferation of MRV in vitro, while knockdown of MRV µ1 protein expression by shRNA could impair MRV proliferation. Specifically, µ1 protein inhibited MRV or poly(I:C)-induced IFN-ß expression, and attenuated RIG-I/MDA5-mediated signaling axis transduction during MRV infection. Importantly, we found that µ1 protein significantly decreased IFN-ß mRNA expression induced by MDA5, RIG-I, MAVS, TBK1, IRF3(5D), and degraded the protein expression of exogenous MDA5, RIG-I, MAVS, TBK1 and IRF3 via the proteasomal and lysosomal pathways. Additionally, we show that µ1 protein can physically interact with MDA5, RIG-I, MAVS, TBK1, and IRF3 and attenuate the RIG-I/MDA5-mediated signaling cascades by blocking the phosphorylation and nuclear translocation of IRF3. In conclusion, our findings reveal that MRV outer capsid protein µ1 is a key factor in antagonizing RLRs signaling cascades and provide new strategies for effective prevention and treatment of MRV infection.

Determination of the half-life of 161Tb.

161Tb has potential applications in targeted radionuclide therapy and nuclear forensic science. However, the half-lives of 161Tb in previous studies show a discrepancy. In this study, 161Tb samples were produced by irradiating 160Gd2O3 with thermal neutron flux. A series of procedures were applied to extract a pure 161Tb solution and three solid samples were prepared. The half-life of 161Tb has been measured with a high-purity germanium (HPGe) detector. The time-dependency of the 161Tb activity was followed by assessing the count rate of their characteristic gamma-ray emissions at 48.9 keV and 74.6 keV over a period of 33-43 days. The experiment and uncertainty budget are discussed in detail. Different uncertainty propagation equations were applied for random uncertainties, medium-frequency deviations and potential systematic errors. The result for the 161Tb half-life of 6.967 (11) d was determined by the weighted mean of half-lives from three samples, which confirms that the half-life is longer than the of the current evaluated half-life of 6.89 (2) d. From all available quoted experimental values, a recommended half-life of 6.934 (14) d was determined by the power-moderated method (PMM). Based on recent four published half-life values, a half-life of 161Tb of 6.9582 (33) d was determined by the PMM analysis.

Chlamydia psittaci pneumonia complicated with organizing pneumonia: A case report and literature review.

A patient with pneumonia had a fever for 2 weeks. After the initial anti-infection treatment failed, he was diagnosed with C. psittaci pneumonia complicated with organizing pneumonia, through next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) and lung biopsy. He was treated with antibiotics and corticosteroids for 2 months.

Pseudorabies Virus ICP0 Abolishes Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Degrading P65.

Nuclear factor κB (NF-κB) is involved in a wide range of innate immune activities in host cells and serves as an important component of a host's immunity system. To survive in infected cells, viruses have evolved intricate strategies to evade the host immune response. Pseudorabies virus (PRV) is a member of the alpha herpesvirus family and is capable of causing reproductive and neurological dysfunction in pigs. PRV has a large DNA genome and therefore has the ability to encode numerous proteins that modulate host innate immune responses. In the present study, we demonstrated that the PRV-encoded immediate early protein ICP0 inhibits the tumor necrosis factor alpha (TNF-α)-mediated NF-κB signaling pathway. An in-depth study showed that ICP0 protein was able to limit NF-κB activation and decreased the expression of inflammatory cytokines interleukin-6 (IL-6) and interleukin 8 (IL-8). In addition, ICP0 blocked the activation of NF-κB through interacting with p65, degrading its protein expression and limiting its phosphorylation. PRV protein ICP0 is shown for the first time to enable escape from innate immune response through the regulation of NF-κB during PRV infection. These results illustrate that PRV ICP0 is able to block NF-κB activation. This mechanism may represent a critical role in the early events leading to PRV infection.

In vivo antitumor effects of carboxymethyl chitosan-conjugated triptolide after oral administration.

The purpose of this study is to evaluate in vitro and in vivo antitumor efficacy and subacute toxicity of triptolide (TP) prodrug, a conjugate between TP and carboxymethyl chitosan (CC). The CCTP conjugate contained 4∼ wt % TP and displayed excellent aqueous solubility (5 mg/mL) as compared to the native TP (17 µg/mL). In vitro cytotoxicity of CCTP conjugate was evaluated by CCK8 assay against human pancreatic cancer (PC) cell lines, showing comparable the half maximal inhibitory concentration (IC50) values to the parent TP. In a mouse model of PC (BxPC-3), the CCTP conjugate administered orally (at dose levels as low as 0.2 mg TP equivalent/kg) showed comparable efficacy in reducing or eliminating xenograft tumor to the same dose of TP, but exhibited much lower subacute toxicity as seen in body weight loss and hematological toxicity.

Huge abdominal and perineal aggressive angiomyxoma: A misdiagnosed case report and literature review.

Aggressive angiomyxoma (AA) is a distinctive soft tissue tumor with a high risk of local recurrence. Clinicians must be aware of this rare tumor pre-operatively. Excision is the preferred method of AA treatment. The case report presents a case of a 36-year-old woman who was difficulty in walking due to a non-painful tumor in the abdomen and perineum. She was misdiagnosed as abdomen neurofibroma for more than 10 years, and an operation was performed in 1997. However, the tumor was incompletely resected because its huge volume accompanies with extensive infiltration and bleeding. The tumors in her abdomen and perineum were growing gradually, and the latter became a large lump which impeded her daily life. In 2008, the perineal tumor was incompletely resected, which weighed 10725 g. The severe hemorrhage had been ceased by Gonadotropin-Releasing Hormone treatment. She is alive till now. Details of the history and operative procedures are presented. An AA diagnosis was made by microscopy immunohistochemically. Long-time misdiagnosis and improper treatment are the important reasons for making it impossible to be radically resected. Pathological and immunohistochemical examination are important for avoiding misdiagnosis. For this case, there is a remaining tumor in her abdomen. A special project including further follow-up and treatment will be taken out.

[The rule of lymphatic formation in rabbit VX2 supraglottic carcinoma model with lymph node metastasis].

OBJECTIVE: Establishment of transplanted model of VX2 supraglottic carcinoma in rabbits and investigation the rule of lymphatic vessels formation. METHOD: After establishment of VX2 tumor-bearing rabbits, the carcinoma tissues were transplanted into the operculum laryngis submucosa in sixty New-Zealand white rabbits to establish transplanted tumor model. Vascular endothelial growth factor-3 (VEGFR-3) label staining was performed to observe lymphatic vessels. Number density, volume density of lymphatics periphery region of carcinoma, normal region and centre region were measured using computer image analysis system. RESULT: There was no lymphatic vessels in carcinomatous centre region,but the lymphatic vessels number density, volume density in periphery region was much more than normal region. Their cavities were dilated. The discrepancy had statistical significance (P<0.01). CONCLUSION: The rule of lymphatic formation in rabbit VX2 supraglottic carcinoma model mimesis rule of lymphatic formation anthropo- supraglottic carcinoma. Lymphatic multiplication and dilation at periphery region of carcinoma is associated with lymph node metastasis. Evaluation of it at periphery region of carcinoma may be useful in predicting lymph node metastasis in patients with supraglottic carcinoma. This conclusion provides theoretical basis for utility of the anti-tumor medicines which inhibit lymphatic formation in animal model.

Prostate stem cell antigen enhancer and uroplakin II promoter based bladder cancer targeted tissue-specific vector.

PURPOSE: To construct a dual specific vector which contains prostate stem cell antigen enhancer (PSCAE) and uroplakin II (UPII) promoter targeted bladder cancer. METHODS: UPII promoter and PSCAE were amplified by polymerase chain reaction (PCR). Luciferase gene (LUC) was obtained from plasmid pBK-CMV-LUC. PSCAE, UPII promoter and LUC were inserted into shuttle plasmid to create Rp-UPII-LUC and Rp-PSCAE-UPII-LUC. Rp-UPII-LUC and Rp-PSCAE-UPII-LUC were cotransfected with pCMV-beta-gal into various cell lines at the presence or absence of androgen receptor agonist R1881 and androgen receptor antagonist flutamide. Luminescence was detected with luciferase assay kit and counted on liquid scintillation counter. RESULTS: Bladder cancer cells showed higher LUC activity than non-bladder cancer cells after transfected with plasmids Rp-UPII-LUC and Rp-PSCAE-UPII-LUC. PSCAE could improve the LUC activity in both AR positive and AR negative bladder cancer cells but not in non-bladder cancer cells and normal human urothelial (NHU) cells. R1881 could increase the LUC activity in AR positive bladder cancer cells but not in AR negative bladder cancer cells and non-bladder cancer cells. Flutamide could not inactivate PSCAE in bladder cancer cells. CONCLUSIONS: PSCAE can improve target gene expression in bladder cancer cells but not in non-bladder cancer cells and NHU cells. PSCAE maintains a certain level of androgen independent activity in bladder cancer cells. PSCAE is active in both AR positive and AR negative bladder cancer cells. The results suggest that combination of PSCAE with UPII promoter is feasible in constructing bladder cancer-specific vectors.