Simulating immunosuppressive mechanism of Microplitis bicoloratus bracovirus coordinately fights Spodoptera frugiperda.

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.

Bracovirus Sneaks Into Apoptotic Bodies Transmitting Immunosuppressive Signaling Driven by Integration-Mediated eIF5A Hypusination.

A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression.

Nuclear Dbf2-related Kinase 1 functions as tumor suppressor in glioblastoma by phosphorylation of Yes-associated protein.

BACKGROUND: The Nuclear Dbf2-related (NDR1) kinase is a member of the NDR/LATS family, which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating Yes-associated protein (YAP) remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. This study aimed to investigate the role of NDR1-YAP pathway in GBM. METHODS: Bioinformation analysis and immunohistochemistry (IHC) were performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing CCK-8, clone formation, immunofluorescence and flow cytometry, respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-immunoprecipitation and immunofluorescence to observe co-localization. RESULTS: Bioinformation analysis and IHC of our patients' tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to a lower survival rate. NDR1 could markedly reduce the proliferation and colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-overexpression group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phosphorylate YAP at S127 site. Meanwhile, NDR1 could mediate apoptosis process. CONCLUSION: In summary, our findings point out that NDR1 functions as a tumor suppressor in GBM. NDR1 is identified as a novel regulator of YAP, which gives us an in-depth comprehension of the Hippo signaling pathway.

Carotid Endarterectomy with Stent Graft Removal and End to End Bypass in the Treatment of In-Stent Occlusion after Endovascular Therapy of Carotid Gunshot Injury.

Carotid jugular fistula and pseudoaneurysm are easy to form after gunshot injury of carotid artery. Endovascular therapy, such as stent graft implantation, can successfully block the fistula and pseudoaneurysm cavity. However, the possibility of in-stent restenosis or occlusion will lead to treatment failure. The authors describe the case of a 30-year-old man with carotid jugular fistula and pseudoaneurysm after gunshot injury of left carotid artery who had received stent graft placement. However, two years after stent graft, the stenosis of proximal carotid artery near stent was found and gradually aggravated. During the follow-up, transient amaurosis of his left eye occurred intermittently and in-stent occlusion and severe stenosis of proximal carotid artery were found by computed tomography angiography (CTA) in our center. Carotid endarterectomy (CEA)with stent graft removal and end to end bypass using vascular graft was performed to reconstruct the blood flow of left carotid artery. To the extent of the authors' knowledge, this case illustrates a rare CEA and vascular graft bypass in the treatment of in-stent occlusion following the gunshot injury to the carotid artery. The successful treatment of this rare case provides an option to deal with this kind of tricky problem.

Interactions of Vank proteins from Microplitis bicoloratus bracovirus with host Dip3 suppress eIF4E expression.

Microplitis bicoloratus bracovirus (MbBV) inhibits the immune response of the host Spodoptera litura by disrupting nuclear factor (NF)-κB signaling and downstream gene expression. However, the underlying molecular mechanisms are not well understood. Herein, we report that viral ankyrin (Vank) proteins interacted with host dorsal-interacting protein 3 (Dip3) to selectively inhibit the transcription of eukaryotic translation initiation factor 4 E (eIF4E). Dip3 and Vank proteins were co-expressed and colocalized in the nucleus. Furthermore, ectopic expression of Dip3 rescued the transcription of some NF-κB-dependent genes suppressed by Vank proteins, including eIF4E. Co-immunoprecipitation and pull-down assays confirmed that Vank proteins interacted with and bound to full-length Dip3, which including MADF, DNA-binding protein, BESS, and protein-protein interaction motifs as well as non-motif sequences. In vivo, RNAi-mediated dip3 silencing decreased eIF4E levels and was accompanied by an immunosuppressive phenotype in S. litura. Our results provided novel insights into the regulation of host transcription during immune suppression by viral proteins that modulate nuclear NF-κB signaling.

Application of pulse index continuous cardiac output system in elderly patients with acute myocardial infarction complicated by cardiogenic shock: A prospective randomized study.

BACKGROUND: Cardiogenic shock (CS) secondary to acute myocardial infarction (AMI) complicates management of the condition, and often leads to poor prognosis. Prompt and accurate monitoring of cardiovascular and accompanying hemodynamic changes is crucial in achieving adequate management of the condition. Advances in technology has availed procedures such as pulse index continuous cardiac output (PiCCO), which can offer precise monitoring of cardiovascular functions and hemodynamic parameters. In this study, PiCCO is evaluated for its potential utility in improving management and clinical outcomes among elderly patients with AMI complicated by CS. AIM: To assess whether use of the PiCCO system can improve clinical outcomes in elderly patients with AMI complicated by CS. METHODS: Patients from emergency intensive care units (EICU) or coronary care units (CCU) were randomized to receive PiCCO monitoring or not. The APACHE II score, SOFA score, hs-TnI, NT-proBNP, PaO2/FiO2 ratio and lactate levels on day 1, 3 and 7 after treatment were compared. The infusion and urine volume at 0-24 h, 24-48 h and 48-72 h were recorded, as were the cardiac index (CI), extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end diastolic volume index (GEDVI) at similar time intervals. RESULTS: Sixty patients with AMI complicated by CS were included in the study. The PiCCO group had a significantly lower APACHE II score, SOFA score, hs-TnI and NT-proBNP levels on day 1, 3 and 7 after treatment. The infusion and urine volume during 0-24 h in the PiCCO group were significantly greater, and this group also showed significantly higher ADL scores. Furthermore, the PiCCO group spent lesser days on vasoactive agents, mechanical ventilation, and had a reduced length of stay in EICU/CCU. Additionally, the CI was significantly higher at 48 h and 72 h in the PiCCO group compared with that at 24 h, and the EVLWI, ITBVI and GEDVI were significantly decreased at 48 h and 72 h. CONCLUSION: Applying the PiCCO system could improve the clinical outcomes of elderly patients with AMI complicated by CS.

Influence of Familiarity on Energy Intake and Plasma Gut Hormone Concentration in Lean and Overweight Young Male Students.

OBJECTIVE: This study is to examine the influence of familiarity on energy intake, eating behavior, and concentration of the plasma gut hormones in lean and overweight young male subjects. METHODS: Twenty-eight lean and twenty-eight overweight participants were recruited. Their food consumption was documented and analyzed when they had a test meal while they were paired with friends or strangers at the same weight stature. Their eating behavior was recorded with cameras hidden in the carton, and postprandial plasma gut hormone concentration were measured. RESULTS: Compared with overweight strangers (OS), overweight friends (OF) had increased food consumption, prolonged and decreased number of chews per 10 g food. Compared with OS, postprandial plasma concentration of cholecystokinin-8 was significantly lower in OF group at 30, 60, and 90 min, whereas the concentration of glucagon-like peptide 1 was significantly lower at 60 and 90 min. Plasma ghrelin concentration was significantly higher in the OF group than that in the OS group at 90 and 120 min. No significant differences in gut hormone concentration were observed between lean strangers (LS) and lean friends (LF) groups at all time points. CONCLUSION: Familiarity plays an important role in increasing energy intake and in changing of postprandial gut hormone concentration in overweight individuals.

Homocysteine is associated with the progression of non-culprit coronary lesions in elderly acute coronary syndrome patients after percutaneous coronary intervention.

BACKGROUND: The influence of homocysteine (Hcy) on the migration and proliferation of vascular smooth muscle cells has been well established. However, the impact of Hcy levels on the progression of non-culprit coronary lesions (NCCLs) is controversial. This study aims to evaluate whether the plasma level of Hcy is related to the progression of NCCLs after percutaneous coronary stent implantation in elderly patients with acute coronary syndrome (ACS). METHODS: A total of 223 elderly patients (≥ 65 years old) with ACS undergoing stent implantation and follow-up coronary angiography were enrolled. Laboratory determination comprised of blood sample evaluation for Hcy was carried out before baseline coronary intervention. The patients were classified into two groups according to the blood Hcy tertiles (≥ 15 mmol/L or < 15 mmol/L). Patients were followed up for 12.2 months. NCCL progression was assessed by three-dimensional quantitative coronary angiography. RESULTS: A significantly higher ratio of NCCL progression was observed in the group with baseline Hcy concentrations above 15 mmol/L compared to the group with concentrations below 15 mmol/L (41/127, 32.3% vs. 14/96, 14.6%, P = 0.002). Multivariate Cox regression analysis showed that Hcy and diabetes mellitus were independent risk factors for NCCL progression. The crude hazard ratio (HR) of NCCL progression for Hcy level was 1.056 (95% CI: 1.01-1.104, P = 0.015). The adjusted HR of NCCL progression for Hcy level was 1.024 (95% CI: 1.007-1.042, P = 0.007). The adjusted HR of NCCL progression for diabetes mellitus was 1.992 (95% CI: 1.15-3.44, P = 0.013). CONCLUSIONS: Hcy is an independent risk factor for NCCL progression after 12 months of follow-up in elderly patients with ACS who has undergone percutaneous coronary stenting.

Relationship between Iodine Content in Household Iodized Salt and Thyroid Volume Distribution in Children.

OBJECTIVE: To assess the effect of different levels of salt iodine content on thyroid volume (ThV) distribution using data from the 1999, 2011, and 2014 Chinese national iodine deficiency disorder (IDD) surveys. METHODS: Probability proportion to size (PPS) sampling method was used to obtain a representative national sample of 34,547, 38,932, and 47,188 Chinese children aged 8-10 years in 1999, 2011, and 2014 Chinese national IDD surveys, respectively. The iodine content in household iodized salt and urinary iodine concentration were measured and thyroid ultrasound examination was performed. The data were analyzed by SAS software using histograms and box plots. The skewness and kurtosis were calculated for testing the normality of ThV. RESULTS: The median iodine content in household iodized salt dropped from 42.30 mg/kg in 1999 to 25.00 mg/kg in 2014. The median urinary iodine concentration of children aged 8-10 years decreased from 306.0 µg/L in 1999 to 197.9 µg/L in 2014. The median and interquartile range (IQR) of ThV in 1999, 2011, and 2014 surveys were 3.44 mL and 1.50 mL, 2.60 mL and 1.37 mL, 2.63 mL and 1.25 mL, respectively. The skewness and kurtosis of ThV distribution in 1999, 2011, and 2014 surveys were 1.34 and 5.84, 0.98 and 3.54, 1.27 and 5.49, respectively. CONCLUSION: With reduced salt iodization levels, the median urinary iodine concentration and median ThV of children decreased significantly, and the symmetry of the ThV distribution improved.

Association of intergenic polymorphism of organic anion transporter 1 and 3 genes with hypertension and blood pressure response to hydrochlorothiazide.

BACKGROUND: Organic anion transporter (OAT) 1 and OAT3, encoded by a tightly linked gene pair, play a key role in renal secretion of diuretics. However, no study has yet examined the influence of OAT1 and OAT3 polymorphisms on high blood pressure (BP) and the response to thiazide diuretics. We hypothesized that intergenic polymorphisms between OAT1 and OAT3 might be associated with adult hypertension and the antihypertensive effects of hydrochlorothiazide (HCTZ). METHODS: The association of an intergenic polymorphism (rs10792367) with hypertension risk was investigated in two independent case-control studies (n = 1,592 and 602), and then a combined analysis was performed for improving power (1,106 cases and 1,088 controls) with adjustment for geographic location. Two clinical trials (n = 542 and 274) were conducted in untreated hypertensive patients for the association of rs10792367 with antihypertensive responses to 4 and 8 weeks of HCTZ treatment. RESULTS: No significant association was found between rs10792367 and hypertension after adjustment for conventional risk factors in either the two populations, respectively, or the combined two population. After adjustment for pretreatment BP and other confounders, HCTZ-induced reduction in systolic BP was 4.8 mm Hg (P = 0.006, first trial) and 6.1 mm Hg (P = 0.003, in second trial) lower, respectively, in C allele carriers than in GG carriers in the two clinical trials. CONCLUSIONS: Intergenic polymorphism rs10792367 between OAT1 and OAT3 is not associated with hypertension, but appears to be involved in between-individual variations in antihypertensive responses to HCTZ.

[Epidemiological study on alcohol consumption and agricultural profession-related injuries among minority residents from the northern parts of China].

OBJECTIVE: To understand the incidence rates of agricultural profession-related injuries and the relationship to alcohol consumption. METHODS: A multistage sample of 2366 villagers was selected from Minority Nationality Villages, Heilongjiang province. Face-to-face interviews were conducted by trained interviewers during May 2008. 2198 (92.9%) of the eligible questionnaires were available. RESULTS: Incidence rate of agricultural profession-related injury rate was 11.8% (260/2198) from May 2007 to April 2008. Higher proportions of injuries were seen for males, 30 - 49 year olds, farmers and among those people working on farms for 10 years or more, smoking during farm work, with sleeping disorder, using motor vehicles, and those using agricultural machinery. Rate of alcohol drinking was 29.1% (640/2198) in the month prior to the investigation. Results from logistic regression models showed that alcohol consumption patterns and other alcohol-related behavior were examined in separate logistic models because of collinearity by controlling the variables that were associated with agricultural profession-related injury including sex, age, years of farm work, driving a motor vehicle, and agricultural machinery use etc. In each model, the reference group was those villagers who did not drink in the past month. The odds of injury among villagers with history of past month drinking, who drank distilled spirits, and alcohol drinking at breakfast and lunch were 1.80 (95%CI: 1.24 - 2.62), 2.09 (95%CI: 1.38 - 3.15), 2.15(95%CI: 1.43 - 3.22) respectively. The odds of agricultural injury also significantly increased with greater average amounts of pure alcohol per day, with increased frequency of drinking per week, and reported years of drinking. CONCLUSION: Intervention efforts should include increasing awareness about alcohol drinking as a major risk factor causing agricultural injuries as well as controlling alcohol drinking, improving knowledge about driving motor vehicle and using agricultural machinery.

Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population.

BACKGROUND: The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population. METHODS: Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Odds ratios were estimated using a case-control study design by controlling confounding factors. RESULTS: The A/A genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41, 95% CI 1.03-1.94), increased waist circumference (OR 1.75, 95% CI 1.26-2.42), and increased fast blood glucose (OR 1.49, 95% CI 1.07-2.06) in women. The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37, 95% CI 1.02-1.84). CONCLUSION: The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.

Cardiovascular risk and prevalence of metabolic syndrome by differing criteria.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in hypertensive population in Chinese countryside is unknown. Firstly, this study compared the prevalence of MetS according to National Cholesterol Education Program (NCEP) ATPIII, revised NCEP and International Diabetes Federation (IDF) definitions. Secondly, it investigated the association between MetS, coronary heart disease (CHD) and stroke in patients with hypertension. METHODS: In this cross sectional study, the cluster sampling method was used. Three MetS definitions were applied to 1418 normal subjects and 5348 hypertensive patients aged 40-75 years in rural areas in China. The agreement between different MetS definitions was estimated by kappa statistics. Logistic regression analyses determined the association between MetS defined by the three MetS definitions and CHD and stroke. RESULTS: In subjects without hypertension, the prevalence of Mets was 4.1% by NCEP definition, 8.3% revised NCEP definition and 7.8% IDF definition. In hypertensive individuals, the prevalence was 14.0%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by the same definitions, respectively. In hypertensive individuals, the agreement was 94.4% in men and 97.0% in women between revised NCEP and IDF definitions. The IDF defined MetS was more strongly associated with CHD than the NCEP or revised NCEP defined MetS (adjusted odds ratio: 1.92 compared with 1.85 and 1.69 in men; 1.64 compared with 1.48 and 1.60 in women). CONCLUSIONS: In the patients with hypertension, the revised NCEP and IDF definitions identified more individuals than NCEP definition and their agreement is very high. The IDF defined MetS is more strongly associated with CHD than the NCEP or revised NCEP defined MetS, but weakly or not associated with stroke.

[The effect and mechanism of felodipine and valsartan on a novel salt-sensitive hypertensive rat induced by sensory denervation].

OBJECTIVE: To investigate the effect and mechanism of valsartan and felodipine extended release tablets (Plendil) on a novel salt-sensitive hypertensive rat induced by sensory denervation. METHODS: Newborn Wistar rats were given 50 mg/kg capsaicin subcutaneously on the 1st and 2nd day of life. Control rats were treated with vehicle solution (10%ethanol, 10%Tween 80 in saline). After weanling period (3 weeks), male rats were divided into 5 groups and subject to the following treatment for 4 weeks: control + high salt diet (4%, CON-HS), capsaicin + normal salt diet (0.5%, CAP-NS), capsaicin + high salt diet (CAP-HS), capsaicin + high salt diet + Valsartan (30 mg/kg per day, by orally) (CAP-HS-VAL), capsaicin + high salt diet + Plendil (30 mg/kg per day, by orally) (CAP-HS-PLE). Tail-cuff systolic blood pressure, body weight, intralymphocytic [Ca(2+)](i), plasma calcitonin gene-related peptide concentration ([CGRP]), angiotensin II concentration ([AngII]) and 24 hour water intake, urinary volume, urinary Na(+) and K(+) concentrations were examined. RESULTS: Tail-cuff systolic blood pressure and intralymphocytic [Ca(2+)](i) were lower in CAP-HS-VAL or CAP-HS-PLE group than those in CAP-HS group. Plasma [AngII] were higher in CAP-HS-VAL group than that in other groups. Tail-cuff systolic blood pressure were lower in CAP-HS-VAL group than that in CAP-HS-PLE group. Intralymphocytic [Ca(2+)](i) were lower in CAP-HS-PLE group than that in CAP-HS-VAL group. The 24 hour urine sodium excretion was higher in CAP-HS-PLE group than that in CAP-HS or CAP-HS-VAL group. CONCLUSION: Valsartan or Plendil could prevent the development of salt-sensitive hypertension induced by sensory denervation and the overloading of intracellular [Ca(2+)](i), which indicated that salt-sensitive hypertension induced by sensory nerve degeneration might be related to renin-angiotensin-aldosterone system (RAAS) and the over loading intracellular [Ca(2+)](i), and might be more closely to RAAS.