Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation.

BACKGROUND: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. METHODS: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model. RESULTS: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs. CONCLUSION: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo. TRANSLATIONAL POTENTIAL STATEMENT: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.

Differential Viral Distribution Patterns in Reproductive Tissues of Apis mellifera and Apis cerana Drones.

Honeybee drones are male bees that mate with virgin queens during the mating flight, consequently transferring their genes to offspring. Therefore, the health of drones affects the overall fitness of the offspring and ultimately the survivability of the colony. Honeybee viruses are considered to be a major threat to the health of honeybees. In the present study, we demonstrated the pattern of common honeybee viruses in various tissues of drones in the western honeybee, Apis mellifera, and the eastern honeybee, Apis cerana. Drones were collected during the mating flight and analyzed using quantitative real-time (qRT-PCR) to detect the presence of seven honeybee viruses. The qRT-PCR result revealed that three honeybee viruses, namely Black Queen Cell Virus (BQCV), Deformed Wing Virus (DWV), and Chinese Sacbrood Virus (CSBV), were detected in the reproductive tissues of A. mellifera and A. cerana drones. The results from qRT-PCR showed that the Israeli Acute Paralysis Virus (IAPV) was only detected in A. mellifera drone body tissues. Moreover, the prevalence of DWV and BQCV in the drones collected from A. mellifera colonies was significantly higher than that of A. cerana. In addition, virus multiple infections were higher in A. mellifera drones compared to those in A. cerana. CSBV was found predominantly in the reproductive tissues of A. cerana drones. This study is the first report describing the presence of the CSBV in reproductive tissues of A. mellifera drones. Our results may reflect the preference of honeybee viruses in honeybee species and may provide a piece of interesting evidence for understanding the virus transmission in A. cerana.

Chinese Sacbrood virus infection in Asian honey bees (Apis cerana cerana) and host immune responses to the virus infection.

Chinese Sacbrood virus (CSBV) is a positive-stranded RNAvirus that infects both the European honey bee (Apis mellifera) and the Asian honey bee (A. cerana). However, CSBV has much more devastating effects on Asian honey bees than on European honey bees, posing a serious threat to the agricultural and natural ecosystems that rely on A. cerana for pollination service. Using quantitative RT-PCR method, we conducted studies to examine the CSBV infection in Asian honey bee colonies and immune responses of individual bees in response to CSBV infection. Our study showed that CSBV could cause infection in different developmental stages of workers including eggs, larvae, pupae, newly emerged workers, and foraging workers. In addition, evaluating the tissue tropism and transmission of CSBV in infected bees showed that CSBV was detected in the ovaries, spermatheca, and feces of queens as well as semen of drones of the same colonies, suggesting an existence of vertical transmission of CSBV in Asian honey bees. Further, the detection of CSBV in colony food suggests that healthy bees could pick the infection by the virus-contaminated food, and therefore, a possible existence of a food-borne transmission pathway of CSBV in Asian bee colonies. The expression analysis of transcripts (defensin, abaecin, apidaecin, and hymenoptaecin) involving innate antiviral immune pathways showed that CSBV infection could induce significant immune responses in infected bees. However, the immune responses to CSBV infection varied among different development stages with eggs exhibiting the lowest level of immune expression and forager workers exhibiting the highest level of immune gene expression. The results obtained in the study yield important insights into the mechanisms underlying disease pathogenesis of CSBV infections in Asian honey bees and provide valuable information for a rational design of disease control measures.

Inflammation-relevant mechanisms for postoperative cognitive dysfunction and the preventive strategy / 中南大学学报(医学版)

Postoperative cognitive dysfunction (POCD) is thought to be a mild cognitive disorder.It means that patients without cognitive diseases before surgery suffer from subtle changes in psychomotility,personality,social skills and cognitive function after the surgery.A decline in memory is the core characteristics of these symptoms.POCD is mainly seen in the elderly people following surgery.It can prolong hospital stay,reduce quality of life,increase mortality,and thus aggravate the burden of public health.It is urgent to take precautions to reduce the incidence.The precise mechanism of POCD remains unclear.Previous studies have shown that inflammation plays an important role in it.Sterile surgery can result in peripheral inflammation.Through several pathways,the signals from the peripheral immune response were sent to central system.Due to the individual difference,the degree of the central neuroinflammation was also heterogeneous.Some inflammations may lead to the occurrence of POCD.In order to prevent POCD,we should focus on the anti-inflammatory therapy.

Prenatal exposure to lipolysaccharide result in expression changes of myocardial renin angiotensin system in offspring rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore expression changes of myocardial renin angiotensin system induced by prenatal exposure to lipopolysaccharide in offspring rats.</p><p><b>METHODS</b>Twelve pregnant SD rats were randomly divided into three groups: LPS model group: intraperitoneal injection of LPS (0.79 mg/kg) at 8, 10, 12 days of pregnancy; control group: intraperitoneal injection of sterile saline (0.5 ml) at 8, 10, 12 days of pregnancy; LPS + PDTC group: intraperitoneal injection of LPS (0.79 mg/kg) at 8, 10, 12 days of pregnancy plus daily intraperitoneal injection of NF-κB inhibitor -pyrrolidine dithiocarbamate (PDTC, 100 mg/kg) on day 8 to 14 pregnancy day. Protein expression of AngiotensinII(AngII) in heart was detected by immunohistochemistry; myocardial ACE,ACE2 mRNA expression was detected by real-time PCR; protein expression of ACE and ACE2 in heart was detected by Western blot in offspring rats of various groups.</p><p><b>RESULTS</b>Compared with control group (0.07 ± 0.02,0.11 ± 0.01), AngII protein levels (0.14 ± 0.04) were significantly increased at 6 weeks (P < 0.01) and 16 weeks (0.17 ± 0.04, P < 0.05) in offspring rats of LPS model group, which could be significantly attenuated by PDTC intervention (0.10 ± 0.01,0.13 ± 0.03, respectively, all P < 0.05).Similarly, myocardial ACE mRNA expression in 16 weeks offspring rats of LPS model group was significantly upregulated compared with control group (1.10 ± 0.26 vs.0.72 ± 0.22, P < 0.05), which was significantly attenuated by PDTC intervention (0.67 ± 0.01, P < 0.01 vs.LPS group). Myocardial protein expression ACE2 in 16 weeks offspring rats of LPS model group was significantly downregulated compared to control group, which was slightly upregulated by PDTC intervention (P > 0.05).</p><p><b>CONCLUSION</b>Pregnancy exposure to lipopolysaccharide increases myocardial ACE and AngII expression while reduces myocardial ACE2 expression in offspring rats, which might be one of the pathomechanisms of offspring hypertension.</p>

Expression and clinical significance of chemokine receptor in peripheral blood mononuclear cells in patients with primary biliary cirrhosis / 第二军医大学学报

0.05),but was correlated with ?-GT(r=-0.295,P