Resumo A proteína 2 de ligação de nucleotídeos de guanina (GNB2) codifica a subunidade β2 (Gβ2) do complexo da proteína G. Tendo em vista o aumento da demanda de biomarcadores em câncer, o presente estudo foi planejado para explorar extensivamente a variação da expressão de GNB2 e seus papéis em diferentes cânceres usando bancos de dados on-line disponíveis e metodologia diversificada. Em vista de nossos resultados, o GNB2 foi notavelmente regulado para cima em relação aos controles correspondentes em 23 tipos de câncer. Além disso, a expressão elevada de GNB2 foi associada à redução da sobrevida global (OS) do carcinoma hepatocelular do fígado (LIHC) e do adenocarcinoma do reto (READ) apenas em todos os tipos de câncer analisados. Isso implica que GNB2 desempenha um papel vital na tumorigênese de LIHC e READ. Várias análises adicionais também exploraram seis vias críticas e poucas correlações relacionadas à expressão de GNB2 e diferentes outros parâmetros, como metilação do promotor, pureza do tumor, infiltração de células T CD8+, alteração genética e drogas quimioterápicas. Em conclusão, o gene GNB2 foi identificado neste estudo como um potencial biomarcador compartilhado (diagnóstico e prognóstico) de LIHC e READ.

Abstract The Guanine-nucleotide binding protein 2 (GNB2) encodes for β2 subunit (Gβ2) of the G-protein complex. Keeping in view the increased demand of reliable biomarkers in cancer, the current study was planned to extensively explored GNB2 expression variation and its roles in different cancers using online available databases and diverse methodology. In view of our results, the GNB2 was notably up-regulated relative to corresponding controls in twenty three cancer types. As well, the elevated expression of GNB2 was found to be associated with the reduced overall survival (OS) of the Liver Hepatocellular Carcinoma (LIHC) and Rectum Adenocarcinoma (READ) only out of all analyzed cancer types. This implies GNB2 plays vital role in the tumorigenesis of LIHC and READ. Several additional analysis also explored six critical pathways and few important correlations related to GNB2 expression and different other parameters such as promoter methylation, tumor purity, CD8+ T immune cells infiltration, and genetic alteration, and chemotherapeutic drugs. In conclusion, GNB2 gene has been identified in this study as a shared potential biomarker (diagnostic and prognostic) of LIHC and READ.

ABSTRACT This study investigated the effects of bamboo vinegar (BV) on production performance, egg quality, antioxidant status, and serum biochemical parameters of laying hens during summer. One hundred twenty 36-week-old Hy-Line Brown laying hens were randomly assigned to 4 groups, with 30 hens per group. The control group was fed a basal diet and 1 mL/kg, 5 mL/kg, and 10 mL/kg BV were added to the basal diet of the 0.1% BV, 0.5% BV and 1.0% BV groups, respectively. The experiment lasted 30 days and showed that the production performance was not significantly affected by the addition of BV (p>0.05). Egg shape index and glutathione peroxidase activity in serum in BV-supplemented groups were significantly increased (p<0.05). The total protein and the albumin content in the 0.1% BV, 0.5% BV, and 1.0% BV groups were significantly increased compared to the control group (p<0.05). These results suggested that dietary BV could improve the antioxidant capacity and the egg shape index of laying hens in summer.

Congenital abnormalities of the biliary system are a consideration in children with biliary symptomatology. The preoperative diagnosis rate is still not satisfactory, despite progresses made in imaging technology, with the potential of biliary tract injury if surgery is indicated. The double gallbladder is a rare developmental abnormality of the biliary tract with several anatomical variations. This abnormality was accurately delineated in a 7-year-old child by MRI/MRCP, allowing the ductal anatomy to be accurately identified and safe laparoscopic cholecystectomies to be performed.

Resumo O cádmio (Cd) é um dos principais tóxicos, que afeta a saúde humana por meio da exposição ocupacional e ambiental. No presente estudo, avaliamos os efeitos protetores dos cogumelos morel contra os danos reprodutivos induzidos pelo Cd em ratos. Para tanto, 30 ratos machos foram divididos em 6 grupos (n = 5 / grupo); o primeiro grupo serviu de controle, o segundo grupo foi tratado com injeção intraperitoneal (i.p) de 1 mg / kg / dia de Cd. O terceiro e o quarto grupos foram cotratados com 1 mg / kg / dia de Cd (i.p) e 10 e 20 mg / kg / dia de extrato de cogumelo morel (por via oral), respectivamente. Os dois grupos finais receberam gavagem oral de 10 e 20 mg / kg / dia de extrato de cogumelo morel sozinho. Após o tratamento por 17 dias, os animais foram sacrificados e os testículos e o epidídimo foram dissecados. Um testículo e epidídimo de cada animal foram processados para histologia, enquanto o outro testículo e epidídimo foram usados para produção diária de esperma (DSP) e ensaio cometa. Nossos resultados mostraram que os cogumelos Cd e morel não têm efeito sobre o peso do animal, mas o Cd diminui significativamente a contagem de DSP e danifica o DNA hereditário, que é revertido em grupos de cotratamento. Da mesma forma, os resultados histopatológicos dos testículos e do epidídimo mostram que os cogumelos morel controlam os danos a esses tecidos. Considerando que o extrato de cogumelo morel sozinho pode aumentar a produção de testosterona. Esses resultados concluem que os cogumelos morel não apenas controlam os danos causados pelo Cd, mas também podem ser usados como um mecanismo de proteção para danos hereditários ao DNA.

Abstract Cadmium (Cd) is one of the major toxicants, which affects human health through occupational and environmental exposure. In the current study, we evaluated the protective effects of morel mushrooms against Cd-induced reproductive damages in rats. For this purpose, 30 male rats were divided into 6 groups (n=5/group), the first group served as the control group, second group was treated with an intraperitoneal (i.p) injection of 1 mg/kg/day of Cd. Third and fourth groups were co-treated with 1 mg/kg/day of Cd (i.p) and 10 and 20 mg/kg/day of morel mushroom extract (orally) respectively. The final 2 groups received oral gavage of 10 and 20 mg/kg/day of morel mushroom extract alone. After treatment for 17 days, the animals were euthanized, and testes and epididymis were dissected out. One testis and epididymis of each animal were processed for histology, while the other testis and epididymis were used for daily sperm production (DSP) and comet assay. Our results showed that Cd and morel mushrooms have no effect on animal weight, but Cd significantly decreases the DSP count and damages the heritable DNA which is reversed in co-treatment groups. Similarly, the histopathological results of testes and epididymis show that morel mushrooms control the damage to these tissues. Whereas the morel mushroom extract alone could enhance the production of testosterone. These results conclude that morel mushrooms not only control the damage done by Cd, but it could also be used as a protection mechanism for heritable DNA damage.

Resumo Infecções do trato respiratório inferior (ITRIs) são as infecções mais comuns entre pacientes internados em unidade de terapia intensiva (UTI). Pseudomonas aeruginosa é a causa mais comum de ITRIs e está associada ao aumento da mortalidade. Diferentes espécies de Pseudomonas exibem diferentes perfis genéticos e resistência variada as drogas. O presente estudo determina a epidemiologia molecular através do método de fingerprinting de DNA e resistência as drogas de P. aeruginosa isoladas de pacientes com LTRIs internados em UTI. Um total de 79 P. aeruginosa isoladas de pacientes com ITRIs internados em UTI foram caracterizados por Polimorfismo de Comprimento de Fragmentos de Restrição (RFLP), DNA Polimórfico Amplificado ao Acaso (RAPD) e PCR Extrapalindrômico Repetitivo (REP-PCR). A resistência aos antibióticos foram determinadas pelos ensaios de concentrações inibitória mínima (MIC), enquanto os genes MDR, blaTEM, blaOXA, blaVIM, blaCTX-M-15 foram detectados pela reação em cadeia da polimerase (PCR). Das 137 Pseudomonas sp isoladas de pacientes de UTI, 57,7% dos isolados foram relatados como P. aeruginosa. A prevalência geral de P. aeruginosa entre os pacientes incluídos foram de 34,5%. A análise RAPD renderam 45 padrões diferentes com 72 clusters com nível de similaridade de 57% a 100%. A análise RFLP renderam 8 padrões diferentes com 14 clusters com 76% a 100% de similaridade. A análise de PCR do REP produziram 37 padrões diferentes com 65 clusters com nível de similaridade de 56% a 100%. Não houveram correlações entre os diferentes padrões de DNA observados entre os três diferentes métodos. Predominantes dos isolados (46,8%) eram resistentes à amicacina. Dos 79 isolados, 60,8% foram positivos para o gene blaTEM e 39,2% foram positivos para o gene blaOXA. P. aeruginosa foi predominantemente isolado de pacientes com ITRIs internados em UTI. A diferença no nível de similaridade observado entre os três métodos de fingerprinting do DNA indica que há alta variabilidade inter-strain. A alta variabilidade genética e os padrões de resistência indicam que devemos monitorar continuamente a tendência na prevalência e resistência a antibióticos de P. aeruginosa, especialmente em pacientes com ITRIs internados em UTI.

Abstract Lower respiratory tract infections (LRTIs) caused by Pseudomonas aeruginosa are the most common infection among hospitalized patients, associated with increased levels of morbidity, mortality and attributable health care costs. Increased resistant Pseudomonas worldwide has been quite meaningful to patients, especially in intensive care unit (ICUs). Different species of Pseudomonas exhibit different genetic profile and varied drug resistance. The present study determines the molecular epidemiology through DNA fingerprinting method and drug resistance of P. aeruginosa isolated from patients with LTRIs admitted in ICU. A total of 79 P. aeruginosa isolated from patients with LRTIs admitted in ICU were characterized by Restriction Fragment Length Polymorphism (RFLP), Random Amplified Polymorphic DNA (RAPD) and Repetitive Extrapalindromic PCR (REP-PCR). Antibiotic resistance was determined by minimum inhibitory concentration (MIC) assay while MDR genes, viz, blaTEM, blaOXA, blaVIM, blaCTX-M-15 were detected by polymerase chain reaction (PCR). Of the 137 Pseudomonas sp isolated from ICU patients, 57.7% of the isolates were reported to be P. aeruginosa. The overall prevalence of P. aeruginosa among the all included patients was 34.5%. The RAPD analysis yielded 45 different patterns with 72 clusters with 57% to 100% similarity level. The RFLP analysis yielded 8 different patterns with 14 clusters with 76% to 100% similarity level. The REP PCR analysis yielded 37 different patterns with 65 clusters with 56% to 100% similarity level. There was no correlation among the different DNA patterns observed between the three different methods. Predominant of the isolates (46.8%) were resistant to amikacin. Of the 79 isolates, 60.8% were positive for blaTEM gene and 39.2% were positive for blaOXA gene. P. aeruginosa was predominantly isolated from patients with LRTIs admitted in ICU. The difference in the similarity level observed between the three DNA fingerprinting methods indicates that there is high inter-strain variability. The high genetic variability and resistance patterns indicates that we should continuously monitor the trend in the prevalence and antibiotic resistance of P. aeruginosa especially in patients with LRTIs admitted in ICU.

ABSTRACT This study was conducted to evaluate the influence of supplementing tea polyphenols (TP) in diet of laying hens on yolk cholesterol content and production performance. A total of 1800 Lohmann laying hens aged 48 weeks were randomly allocated to 6 groups. Each group consisted of 6 replicates with 50 layers. The feeding experiment was 4 weeks including one-week acclimatization. Layers fed basal diet supplemented with 0, 150, 200, 250, 300 and 350 mg TP/kg diet, respectively. The results showed that average daily feed intake (ADFI), feed conversion ratio (FCR), average egg weight (AEW), laying rate and the indicators of egg quality were not significantly affected by the diet supplemented with 300 mg/kg TP (p>0.05). However, yolk cholesterol content decreased by increasing TP concentration (p<0.01), with 18.06% reduction in layers fed diet supplemented with 300 mg TP/kg. Also, the diet supplemented with 300 mg/kg TP significantly decreased plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) level (p<0.05). The activity of serum glutathione peroxidase (GSH-Px) was enhanced by increasing TP concentration, while the content of serum methane dicarboxylic aldehyde (MDA) was decreased by increasing TP concentration. The highest activity of GSH-Px and the lowest serum MDA content were both determined in 300 mg/kg TP group (p<0.01). In conclusion, this study suggests that the addition of 300 mg TP/kg basal diet had no negative effect on the production performance laying hens, yet decreased the egg yolk cholesterol content and enhanced the antioxidant capacity of laying hens at the same time.

RESUMO Utilizando um anticorpo monoclonal contra a aflatoxina B1 (AFB1) como ligante, foi identificado um mimotopo específico de aflatoxina B1 após se realizarem quatro ciclos de seleção biológica de 7-peptídeos aleatórios em biblioteca de fago exibida. O mimotopo é denominado P10, e sua sequência de aminoácidos é YRRHEKD. O soro imunológico de ratos Balb/c imunizados com P10 foi especificamente ligado à aflatoxina B1-albumina, indicando que o anticorpo era específico ao AFB1. Esses resultados sugerem que é possível desenvolver a vacina baseada em mimotopo associado à toxina.

ABSTRACT To investigate the effects of soy isoflavones (ISF) on the laying performance of Xueshan breeder hens at different phases of the egg production cycle, 32 weeks (wks) old local Chinese breeder hens were assigned to two groups with three replicates (750 hens/replicate) for control and treatment groups. Then every group was divided into three sub-groups following 4, 12, and 20 wks administration of control or ISF diet. General Linear Model procedure was used (2× 3), and treatments were considered of two factors (diets and time) with different levels (control and ISF diets; 4, 12, and 20 wks of diet supply time). Basal diet with 3 mg/kg ISF was used. Performance, egg quality, organs relative weight and cholesterol level were measured at three time-points of 36, 44, and 52-wks of age old. The results showed that both diets and time significantly affected the production performance and physiological parameters. In details, ISF inclusion significantly (p=0.02) decreased average egg weight and average feed intake compared to control at 52-wks of age old, however, feed conversation ratio was not affected by ISF diet. Moreover, ISF diet caused to an increase hatching rate (p=0.01) at 36-wks old hens, an abnormal egg rate decrease (p=0.02) at 44-wks old, an increase in yolk color (p=0.035) and Haugh unit (p=0.039), and a decrease in low-density lipoprotein cholesterol level (p=0.03) at 52-wks of age old. ISF diet also increased spleen relative weight (p=0.041) and total antioxidant capacity compared to the control group. The results revealed that ISF inclusion exerted some benefits, thus it could be a potential feed additive for the breeder hens.

ABSTRACT This study was conducted to establish dietary threonine (Thr) levels for Linwu ducks, aged 4 to 8 wk. Experimental diets formulated to contain 0.56, 0.61, 0.66, 0.71, 0.76, and 0.81% Thr fed to Linwu ducks. A total of 360 healthy Linwu female ducks with similar body weight (1183.89±3.83 g) were randomly divided into six groups, with five replicates in each group, and 12 ducks in each replicate. Samples were collected at 8 wk for the determination of growth performance, carcass traits, visceral organ indices, and serum biochemical parameters. As a result of this study, Thr level had no significant influence on the final weight, the daily gain, feed/gain ratio, and average daily intake (p>0.05). Similarly, there were no significant effects of dietary Thr on carcass traits and visceral organ indices (p>0.05). The pancreatic index was highest among all the treatments when the dietary Thr level was 0.66%. The different dietary Thr levels had no significant effect (p>0.05) on the concentration of total protein (TP), triglyceride (TG), total cholesterol (TC), glucose (GLU), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and glutathione (GSH). However, the serum MDA concentration in the 0.66% treatment was lower (P=0.068) than in the other treatments. In conclusion, Thr at 0.66% concentration may have an antioxidant activity and exert positive effect on Linwu ducks.

ABSTRACT This study was carried to express the interferon-induced transmembrane protein 3 (IFITM3) in vitro and examine its function in inhibition of avian reovirus (ARV) replication. The recombinant prokaryotic vector expressing yellow-feathered broiler IFITM3 was successfully constructed, and the recombinant protein was expressed in competent Escherichia coli BL21 cells. New Zealand white rabbits were immunized with the purified recombinant protein to prepare a polyclonal antibody, with a titer of 1:128,000. Immunohistochemistry, reverse transcription-PCR, and real-time fluorescence quantitative PCR showed that IFITM3 was distributed in the yellow-feathered broiler immune organs, and the expression of IFITM3 in bursa of Fabricius was more than in spleen and thymus. It was found that in the thymus, spleen and bursa of Fabricius the mRNA expression levels of IFNα and IFITM3 were significantly induced after ARV infection. And it was also certified in the chicken embryo fibroblasts (CEFs) which infected with ARV. Then the IFNα was added into the cell culture medium before CEFs were infected with ARV. The results indicated that the mRNA of IFITM3 expression was significantly increased and ARV multiplication was significantly inhibited. And when the expression of IFITM3 was knocked down by siRNA-IFITM3, the expression of IFITM3 was significantly reduced, but the ARV multiplication was significantly increased, which indicated that IFITM3 protein could inhibit the ARV replication.

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

Vitamin D (25(OH)D3) is an essential nutrient that plays a role in the immune system. Serum 25(OH)D3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3–4 weeks old) into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OH)D3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF) cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OH)D3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

ABSTRACT In order to investigate the effect of organic trace minerals premix (OTM) on the reproductive performance of breeder roosters, a total of 240 San Huang roosters (23 weeks of age) were randomly divided into two treatments with six replicates of 20 roosters each. The first group (n = 120) was fed a basal diet containing an inorganic trace minerals premix (ITM) and the other group (n = 120) was fed the basal diet in which ITM was replaced by OTM. The experiment period was 22 weeks. Semen from one randomly-selected rooster per replicate was collected two weeks after the beginning of the experiment and other 10 times every two weeks. Another rooster per replicate was randomly selected at 30, 35, and 45 weeks of age, and sacrificed. Results showed that OTM did not affect relative organ weights. There was a significant increase in semen parameters in OTM group (p<0.05), such as semen volume, semen density, and semen motility from 31 to 35 weeks. OTM-fed roosters presented higher serum testosterone levels at 45 weeks of age, as well as higher testicular mRNA expression of the genes 3-beta dehydrogenase 2 (HSD3B2) and cytochrome P450 17A1 (CYP17A1) in the OTM-fed group at 45 weeks of age compared with those fed ITM (p<0.05). Considering the results of the present study, it was concluded that feeding organic instead of inorganic trace minerals to male broilers breeders improves semen quality, which may be attributed to their better testicular development and higher expression of enzymes related to testosterone synthesis.

The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA). A total of 23 sJIA patients (13 males, median age 8.2), 20 acute lymphoblastic leukemia (ALL) patients, 18 patients with severe infections (SIF), 26 Kawasaki disease (KD) patients, 18 juvenile idiopathic arthritis (JIA) patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA). The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases.