Assuntos
Leucemia Mieloide Aguda , Complexo de Proteínas Formadoras de Poros Nucleares , Humanos , Leucemia Mieloide Aguda/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Masculino , Proteínas de Ligação a Poli-ADP-Ribose/genética , Pálpebras/anormalidades , Rearranjo Gênico , Proteínas Oncogênicas/genética , Proteínas Cromossômicas não HistonaRESUMO
Objective: To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC). Methods: Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups. Results: The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group (P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ2=6.247, P=0.012). Conclusion: EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.
Assuntos
Gastrectomia , Recidiva Local de Neoplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Feminino , Masculino , Estudos Retrospectivos , Prognóstico , Adulto , Pessoa de Meia-Idade , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico , Metástase Linfática , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ2=5.442,P<0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Estudos de Casos e Controles , Neoplasias Gástricas/cirurgia , Patologia Molecular , Herpesvirus Humano 4 , ClaudinasRESUMO
Fumonisins (FUM) and deoxynivalenol (DON) are two common mycotoxins in poultry feed. Salmonella enterica ser. Enteritidis (S. Enteritidis) is a primary foodborne bacterium in broilers. This trial was conducted to evaluate the effects of naturally occurring FUM and DON and their combination at subclinical doses on broiler performance during a S. Enteritidis challenge. The experiment consisted of five treatments: NCC, no-challenge no-mycotoxin treatment; CC, Salmonella challenge + no-mycotoxin treatment; DON, DON 0.6 mg/kg + Salmonella challenge; FUM, FUM 14 mg/kg + Salmonella challenge; DON + FUM + T-2 + neosolaniol, DON 0.6 mg/kg + FUM 14 mg/kg + T-2 toxin 0.6 mg/kg + 0.8 mg/kg neosolaniol + Salmonella challenge. On d 4, birds were challenged with either 0 or 1 × 109 CFU/mL S. Enteritidis orally. There were no significant effects on growth performance among treatments at 0, 3, 7, and 14 d of post-inoculation (dpi). On 14 dpi, the combined DON + FUM + T-2 + neosolaniol significantly increased the Salmonella load by 1.5 logs compared to the control groups (P < 0.05). FUM significantly increased the cecal tonsil IL-10 gene expression by 1.2-fold at 7 dpi (P < 0.05) and downregulated TNF-α by 1.8-fold on 14 dpi compared to the control, nonchallenge groups (P < 0.05). On 7 dpi, the combined DON + FUM + T-2 + neosolaniol reduced occludin by 4.4-fold (P < 0.05) when compared to the control groups. Similarly, combined DON + FUM+ T-2 + neosolaniol decreased zona-occluden transcription by 2.3 and 7.6-fold on 3 and 14 dpi, respectively (P < 0.05). Furthermore, combined DON + FUM + T-2 + neosolaniol decreased Claudin-1 by 2.2-fold and Claudin-4 by 5.1-fold on 14 dpi when compared to the control groups (P < 0.05). In conclusion, short-term exposure to a subclinical dose of combined DON + FUM + T-2 + neosolaniol had an impact on broiler intestinal tight junction proteins and cecal Salmonella abundance under experimental Salmonella challenge.
Assuntos
Fumonisinas , Micotoxinas , Doenças das Aves Domésticas , Salmonelose Animal , Animais , Ração Animal/análise , Galinhas , Fumonisinas/toxicidade , Micotoxinas/toxicidade , Doenças das Aves Domésticas/microbiologia , Salmonella enteritidis , Salmonelose Animal/microbiologiaRESUMO
Objective: To compare the efficacy and safety of Tonghua Dongbao's insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes. Methods: A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3â¶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment. Results: For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% (P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % (P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95%CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% (P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% (P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L (P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L (P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group (P=0.320). Ratios of negative to positive were 7.43% and 10.61% (P=0.360), and ratios of positive to negative were 10.40% and 7.58% (P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% (P=0.371), and the incidence of adverse events was 76.60% and 77.70% (P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions: Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.
Assuntos
Diabetes Mellitus Tipo 2 , Insulina Aspart , Glicemia , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Insulina Aspart/efeitos adversos , Insulina GlarginaRESUMO
Objective: To explore the effect and related regulatory mechanism of hawthorn leaf flavonoids (FHL) on cardiac function in rats with acute myocardial infarction (AMI). Methods: Sixty SPF male Sprague-Dawley rats (9-week-old, weighing 300-350 g) were used in this study. Ten rats were assigned to sham operation group, and the remaining 50 rats were used to establish the AMI model with coronary artery ligation method, AMI was successfully established in 36 rats. AMI rats were randomly divided into AMI group and FHL low-, medium-, and high-dose groups (n=9 for each group). Rats received intraperitoneal injection (10 ml·kg-1·day-1) with physiological saline and FHL solution with concentrations of 0.3, 0.6, and 1.2 mg/ml, respectively for 4 consecutive weeks. Echocardiography was performed at the end of experiments. Left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic anterior wall thickness (LAWD), left ventricular ejection fraction (LVEF) and left ventricular end diastolic pressure (LVEDP) were measured. Then the rats were sacrificed under deep anesthesia, and the left ventricular anterior wall tissue was used for pathological examinations by hematoxylin-eosin (HE) staining. Other myocardial tissue was used for in situ terminal transferase labeling (TUNEL) staining, and the apoptosis rate of cardiomyocytes was calculated. The myocardial cell apoptosis rate, the mRNA, and protein expressions of phosphatidylinositol 3ß-kinase (PI3K), protein kinase B (Akt), glycogen synthetase kinase-3 (GSK3ß), cyclin D1 and the protein expressions of p-Akt and p-GSK3ß were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot respectively. Results: Compared with sham operation group, the LVEDD and LVEDP of the rats in AMI group and FHL low-, medium-and high-dose groups were increased, and the LAWD and LVEF were reduced (all P<0.05). Compared with AMI group, LVEDD and LVEDP were reduced, and LAWD and LVEF were increased in FHL low-, medium-and high-dose groups (all P<0.05). LVEDD and LVEDP decreased, and LAWD and LVEF increased in proportion to the increase of FHL dose (all P<0.05). LVEDD and LAWD values were similar between FHL low-dose and medium-dose groups (both P>0.05). HE staining results evidenced necrotic myocardial tissue, together with disordered arrangement of myocardial fibers, and a large number of inflammatory cells infiltrated in the myocardial tissue in AMI group. The myocardial damage of rats in FHL low-, medium-, and high-dose groups was less than that of AMI group. The myocardial fibers were arranged neatly, but there were still partial breaks and a small amount of inflammatory cell infiltration in the myocardial tissue and there were scattered islands of normal myocardial tissue in the infarct area of these groups. Among them, myocardial damage was the least in FHL high-dose group. The results of TUNEL staining showed that compared with AMI group, the apoptosis rate of myocardial cells was significantly reduced in FHL low-, medium-, and high-dose groups (all P<0.001), but was still higher than that in sham operation group (all P<0.001). Myocardial cell apoptosis rate decreased in proportion with increasing FHL dose (P<0.05). The RT-qPCR results showed that compared with AMI group, the expression levels of PI3K and cyclin D1 mRNA were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and PI3K and cyclin D1 mRNA expression levels increased with the increase dose of FHL (P<0.05). Western blot results showed that compared with AMI group, the expression levels of PI3K, p-Akt, p-GSK3ß, and cyclin D1 were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and the protein expression levels of PI3K, p-Akt, p-GSK3ß, and cyclin D1 increased in proportion with the increase dose of FHL (all P<0.05). Conclusion: FHL can effectively improve cardiac function in rats with AMI, and the beneficial effects may be partly mediated through activating PI3K/GSK3ß/cyclin D1 signaling pathway.
RESUMO
This study evaluated the effects of the mycotoxins deoxynivalenol (DON), fumonisins (FUM), and their combination on growth performance, nutrient, and energy digestibility in broilers. A total of 960 Cobb-Cobb male broilers were obtained on the day of hatch and placed 10 birds per cage with 8 cages per treatment. The experiment consisted of 12 treatments: control; DON 1.5 mg/kg; DON 5.0 mg/kg; FUM 20.0 mg/kg; DON 1.5 mg/kg + FUM 20.0 mg/kg; and DON 5.0 mg/kg + FUM 20 mg/kg. The remaining dietary treatments were the correlative nitrogen-free diets (NFD) for determining the endogenous nutrients loss. All birds were fed with a corn-soybean meal diet from days 1 to 15, until birds from latter 6 treatments were switched to their correlative NFD diet from days 15 to 21. Feed and BW were weighed by cage on days 8, 15, and 21. On day 21, ileal digesta was collected for digestibility determination. Both DON 1.5 mg/kg + FUM 20 mg/kg and DON 5.0 mg/kg + FUM 20 mg/kg treatments showed reduced feed intake (P ≤ 0.05) from days 8 to 15 and days 15 to 21. However, no significant effects were noted for BW gain or mortality-adjusted feed conversion ratio after adding single or combined mycotoxin on days 8 and 15. At day 21, cumulative BW gain was less (P ≤ 0.05) in birds fed with the mycotoxin combination diets than the control. No significant changes were shown for ileal endogenous amino acids losses. Control treatment had significantly higher (P ≤ 0.05) apparent ileal energy digestibility than the DON 5.0 mg/kg + FUM 20.0 mg/kg treatment (3,126 vs. 2,895 kcal/kg), representing a 5%-unit loss in apparent DM digestibility. No significant difference was found for standardized crude protein and amino acid digestibility. In conclusion, the combination of DON and FUM (DON 1.5 mg/kg + FUM 20 mg/kg or DON 5.0 mg/kg + FUM 20 mg/kg) reduced DM and ileal energy digestibility, which negatively affected BW gain in broilers.
Assuntos
Galinhas/crescimento & desenvolvimento , Fumonisinas/toxicidade , Tricotecenos/toxicidade , Aminoácidos/metabolismo , Ração Animal/toxicidade , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Galinhas/fisiologia , Dieta/veterinária , Digestão/efeitos dos fármacos , Masculino , Proteínas/metabolismo , Tricotecenos/administração & dosagemRESUMO
This study was conducted to evaluate the effect of an encapsulated sodium butyrate (Na-B) with targeted releasing times on growth performance and mitigating the impact of necrotic enteritis in broilers. Two Na-B (30% of Na-B content) products, CMA (2 h releasing time) and CMP (3 to 4 h releasing time), were evaluated in a necrotic enteritis challenge model. The experiment consisted of 4 Na-B treatments (500 and 1,000 ppm of each product) plus 2 control (non-challenged and challenged). A total of 336 Cobb-Cobb male broilers were placed 8 birds per pen into 7 replicate battery cages. On day 14, birds from challenged treatments were orally gavaged with â¼5,000 oocysts of Eimeria maxima. On day 19, 20, and 21, the challenged birds received 1 mL of 108 cfu/mL Clostridium perfringens. Total pen body weight (BW) and feed weight were assessed on day 14, 21, and 28 for BW gain and mortality-adjusted feed conversion ratio (FCR). On day 21, 3 birds were randomly selected per pen and scored for intestinal lesions. The duodenum and jejunum tissue were collected on day 21 and 28 for quantifying intestinal histology. Results revealed that adding CMA at 500 ppm showed significantly higher cumulative BW gain (P < 0.05) compared to the challenged control from day 1 to 21. Adding CMA at 500 ppm also showed the equivalent cumulative FCR that was comparable to the non-challenged control on day 21. The CMA treatments and CMP at 1,000 ppm treatment showed equivalent BW gain compared to the non-challenge control after an additional 7 d post-challenge on day 28. Both products at 500 or 1,000 ppm had the significantly (P < 0.05) lower intestinal lesion scores compared to the challenged control. However, there was no difference in lesion scores among the Na-B treatments. The Na-B product targeted to release in the anterior intestinal tract shows the beneficial effects on BW gain and feed utilization efficiency in current challenge model. Adding encapsulated Na-B product has the potential to mitigate the impact of necrotic enteritis in broilers.
Assuntos
Ácido Butírico/farmacologia , Enterite/prevenção & controle , Necrose/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Animais , Peso Corporal/efeitos dos fármacos , Ácido Butírico/administração & dosagem , Galinhas , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Clostridium perfringens/fisiologia , Coccidiose/prevenção & controle , Coccidiose/veterinária , Preparações de Ação Retardada , Eimeria/fisiologia , Enterite/veterinária , Intestinos/patologia , Masculino , Necrose/veterinária , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/parasitologiaRESUMO
OBJECTIVE: To investigate the regulatory effect of miR-328 on biological behaviors of hepatocellular carcinoma (HCC) cells, such as invasion and proliferation. PATIENTS AND METHODS: The expressions of miR-328 were detected in 48 pairs of HCC tissue samples and matched adjacent tissues, as well as in 3 kinds of HCC cell lines via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Further, we analyzed the effects of miR-328 inhibition on cell invasion, proliferation, cell apoptosis, and cell cycle. Dual-luciferase activity assay was performed to examine the potential target gene PTEN which was predicted by an online database. Protein levels were detected using Western blot assay. RESULTS: The expression of miR-328 was significantly increased in HCC tissue samples. Decreased miR-328 in HCC cells significantly attenuated cell invasion and proliferation capacities, promoted cell apoptosis and induced cell cycle arrest at G0/G1 phase. Moreover, PTEN was verified as a target gene of miR-328 by dual-luciferase activity assay, qRT-PCR and Western blot. Furthermore, the silence of PTEN neutralized the suppressive effect of decreased miR-328 on cell growth and metastasis. CONCLUSIONS: MiR-328 is involved in the development of HCC via regulating PTEN, which might provide a new target for HCC diagnosis and therapy.
Assuntos
Carcinoma Hepatocelular/enzimologia , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas/enzimologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/secundário , Pontos de Checagem do Ciclo Celular , Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/genética , Transdução de SinaisRESUMO
Two experiments were conducted to determine the effect of an encapsulated sodium butyrate (Na-B) with targeted releasing times on broiler performance, energy digestibility, intestinal morphology, and ceca Salmonella colonization. In experiment 1, 3 different Na-B products (CMA, CMP, and CMS) were evaluated following a challenge with a nalidixic acid-resistant Salmonella typhimurium (STNAR). Cobb-Cobb male birds were placed 8 per pen into 6 replicates for each treatment. Treatments included 6 Na-B treatments (500 and 1,000 ppm of each product) plus 2 control (non-challenged and challenged). Birds were orally gavaged with 0.1 mL of 107 cfu/mL STNAR on d 4. Ceca and ileal samples were collected on d 11. In experiment 2, CMA and CMP products were evaluated for a full grow-out period without an external challenge. Cobb-Cobb male birds were distributed among 45 floor pens with 24 birds per pen. Treatments included 4 product treatments (500 and 1,000 ppm of each product) plus one control. Feed intake and pen weight were obtained on d 14, 28, and 42. Experiment 1 showed that CMP at 1,000 ppm had the highest value for BW and BWG on d 4 (P = 0.07). Adding CMA and CMP at 500 ppm increased ileal digestibility energy (IDE) compared to the challenged control (P ≤ 0.05). The Salmonella recovery data indicated that the challenge had a significant but mild impact, since it did not affect the performance variables but did result in a significant increase in log10 cfu/g cecal material between the non-challenged and challenged control (1.42 vs 3.72). Experiment 2 showed that both products improved the villus height in the duodenum on d 21 (P = 0.08) and IDE on d 42, relative to the control (P ≤ 0.05). This study demonstrates that Na-B has the potential to improve growth in broilers at an early age. The beneficial effects on intestinal morphology and IDE are affected not only by dosage level, but also by the product's releasing time.
Assuntos
Ácido Butírico/metabolismo , Galinhas/fisiologia , Metabolismo Energético/efeitos dos fármacos , Trato Gastrointestinal/crescimento & desenvolvimento , Salmonelose Animal/microbiologia , Ração Animal/análise , Animais , Ácido Butírico/administração & dosagem , Cápsulas , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Masculino , Distribuição Aleatória , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/fisiologiaRESUMO
OBJECTIVE: To study the effects and associated mechanisms of caffeine on cell viability, cycle dynamics, proliferation and apoptosis both in glioblastoma C6 and U87MG cells. MATERIALS AND METHODS: Cell livability in presence or absence of caffeine was detected by the methyl thiazolyl tetrazolium (MTT) colorimetric assay. Flow cytometric analysis was conducted to investigate the cell cycle dynamics and Cell Counting Kit-8 (CCK-8) was used to further study the proliferation of C6 and U87MG glioblastoma cells after treated with caffeine or DMSO. To study the influence of caffeine on apoptosis of glioblastoma C6 and U87MG cells, the value of apoptosis ratio (AR) was calculated by flow cytometry detection. Western blot analysis was used to detect the expression of apoptosis-related factors, including Caspase-3, Cyt-C, Bax and Bcl-2. RESULTS: Caffeine at 1 mM reduced the cell viability of the both rat C6 and human U87MG glioblastoma cells to less than 70%. Flow cytometry detection found that caffeine remarkably arrested the C6 and U87MG cells in G0/G1 phase (C6, U87MG: p<0.01, p<0.05). Nevertheless, the percentage of cells in S phase obviously decreased in the caffeine-treated group, when comparing to that of the normal control (C6, U87MG: p<0.01, p<0.01). CCK-8 assay demonstrated that significant decreases in the number of glioblastoma cells were observed in caffeine treatment group, when comparing to that of the normal control (C6, U87MG: p<0.01, p<0.05). Flow cytometric analysis also found that the application of caffeine induced much higher apoptosis of glioblastoma cells, compared with the normal control (C6, U87MG: p<0.01, p<0.05). Furthermore, caffeine markedly reduced the expression of Bcl-2 (C6, U87MG: p<0.01, p<0.01), and promoted the expression of Cyt-C (C6, U87MG: p<0.05, p<0.01) and Caspase-3 (C6, U87MG: p<0.01, p<0.01), comparing to the normal control. CONCLUSIONS: Caffeine inhibits proliferation and induces apoptosis of C6 and U87MG cells, leading to an imbalance in the ratio of proliferation and apoptosis. The apoptosis might be promoted by the motivation of the caspase-3 signaling pathway, which is induced by the release of Cyt-C as well as the elevated rate of Bax/Bcl-2.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Cafeína/farmacologia , Caspase 3/metabolismo , Glioblastoma/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Glioblastoma/enzimologia , Glioblastoma/patologia , Humanos , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
This experiment was conducted to evaluate the chemical composition and amino acid (AA) digestibility of sunflower seed meal (SFSM) and to use this data to develop prediction equations for estimating AA digestibility for growing pigs. Ten SFSM were collected from five provinces in China. Twelve barrows (38.8±4.6 kg), fitted with ileal T-cannula were allotted into two 6×6 Latin square designs. Each of six experimental periods comprised a 5-d adaption period followed by a 2-d collection of ileal digesta. The ten test diets contained 50% SFSM as the sole source of AA. Another nitrogen-free diet was used to measure the basal endogenous losses of crude protein (CP) and AA. Chromic oxide (0.3%) was used as an inert marker in each diet. There was considerable variation (CV>10%) among the ten SFSM in chemical composition (dry matter [DM]). The concentration of CP and ether extract (EE) ranged from 29.33% to 39.09% and 0.88% to 11.33%, respectively. Crude fibre (CF), neutral detergent fibre and acid detergent fibre ranged from 21.46% to 36.42%, 38.15% to 55.40%, and 24.59% to 37.34%, respectively. There was variation among the ten SFSM in apparent ileal digestibility (AID) and standardized ileal digestibility (SID) for lysine and threonine, which ranged from 63.16 to 79.21 and 55.19% to 72.04% for AID and 67.03% to 82.07% and 61.97% to 77.01% for SID, respectively. The variation in CP and methionine ranged from 60.13% to 74.72% and 74.79% to 88.60% for AID and 66.70% to 79.31% and 77.16% to 90.27% for SID, respectively. Methionine was a good indicator to predict AA digestibility. These results indicate that conventional chemical composition of SFSM was variable (CV>10%) among the ten SFSM (DM). The results of AID, SID and prediction equations could be used to evaluate the digestibility of SFSM in growing pigs.
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The purpose of this experiment was to determine and compare the digestibility of crude protein (CP) and amino acids (AA) in full-oil (no oil extracted) and de-oiled (oil extracted) corn distillers dried grains with solubles (DDGS) with different condensed distillers solubles (CDS) ratios. Six barrows (29.6±2.3 kg) fitted with ileal T-cannula were allotted into a 6×6 Latin square design. Each period was comprised of a 5-d adaption period followed by a 2-d collection of ileal digesta. The five test diets contained 62% DDGS as the sole source of AA. A nitrogen-free diet was used to measure the basal endogenous losses of CP and AA. Chromic oxide (0.3%) was used as an index in each diet. The results showed that CP and AA were very similar in 5 DDGS, but the standardized ileal digestibility (SID) of lysine (from 56.16% to 71.15%) and tryptophan (from 54.90% to 68.38%) had the lowest values and largest variation within the essential AA, which suggests reduced availability of AA and different levels of Maillard reactions in the five DDGS. The apparent ileal digestibility and SID of CP and most of AA in full-oil DDGS (sources 1 and 2) were greater (p<0.05) than de-oiled DDGS (sources 3, 4, and 5). Comparing the AA SID in the 5 DDGS, full-oil with low CDS ratio DDGS (source 1) had non-significantly higher values (p >0.05) than full-oil with high CDS ratio DDGS (source 2); however, the SID of most AA of de-oiled with low CDS ratios DDGS (source 3) were non-significantly lower (p>0.05) than de-oiled with high CDS ratio DDGS (source 4); and the de-oiled DDGS with middle CDS ratio (source 5) but with different drying processing had the lowest SID AA values. In conclusion, de-oiled DDGS had lower SID of CP and AA than full-oil DDGS; a higher CDS ratio tended to decrease the SID of AA in full-oil DDGS but not in de-oiled DDGS; and compared with CDS ratio, processing, especially drying, may have more of an effect on AA digestibility of DDGS.
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This study aimed to investigate the influence of hypercholesterolemia (HC) on intracellular calcium ion concentration in the sphincter of Oddi (SO) of rabbits and the influence of paeoniflorin on intracellular calcium ion concentration in the hypercholesterolemic rabbit SO. Sixteen purebred New Zealand rabbits were randomly divided into two groups: the control group and the HC model group (8 rabbits in each group). The control group was fed standard diet. The HC group was fed standard diet plus cholesterol for a total of 8 weeks to induce and establish the rabbit HC model. The SO segment of HC rabbits was taken and enzyme treated to obtain SO cells. After primary culture, immunohistochemical analysis was performed. Fluo-3/AM was used to load SO cells, and then intracellular calcium ion concentration was determined by confocal microscopy. Intracellular calcium ion in the SO of the HC group was higher than that of the normal group; intracellular calcium ion in the HC rabbit SO of the paeoniflorin group was lower than that of the control group, where the paeoniflorin effect was greater with higher concentrations. High cholesterol caused an increase in intracellular calcium ion concentration in the rabbit SO, and paeoniflorin can reduce intracellular calcium ion concentration in the HC rabbit SO in a concentration-dependent manner.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cálcio/metabolismo , Células Epiteliais/efeitos dos fármacos , Glucosídeos/farmacologia , Hipercolesterolemia/metabolismo , Monoterpenos/farmacologia , Esfíncter da Ampola Hepatopancreática/efeitos dos fármacos , Compostos de Anilina , Animais , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Corantes Fluorescentes , Hipercolesterolemia/patologia , Transporte de Íons/efeitos dos fármacos , Masculino , Cultura Primária de Células , Coelhos , Esfíncter da Ampola Hepatopancreática/metabolismo , Esfíncter da Ampola Hepatopancreática/patologia , XantenosRESUMO
Forsythia suspensa extract (FSE) has been demonstrated to attenuate physiological stress induced by high temperature or high stocking density. This experiment was conducted with 144 male Arbor Acre broilers (1-d-old, weighing 42.7 ± 1.7 g) to determine the effects of FSE on performance, nutrient digestibility, antioxidant activities, serum metabolites, and immune parameters for birds treated with corticosterone (CS). The birds were randomly allotted to 1 of 4 treatments in a 2 × 2 factorial arrangement that included FSE supplementation (0 or 100 mg/kg) and CS administration (0 or 20 mg/kg of diet for 7 consecutive days starting on d 14). The feeding program consisted of a starter diet from d 1 to 21 and a finisher diet from d 22 to 42. Corticosterone administration decreased (P < 0.01) ADG and impaired (P < 0.01) feed conversion ratio in both phases and overall, which were alleviated (P < 0.01) by dietary FSE supplementation in the finisher phase and overall. At d 21, CS administration caused decreases (P < 0.05) in the apparent digestibility of energy, relative weight of bursa and thymus, total antioxidant capacity, superoxide dismutase (SOD) activity, and antibody titers to Newcastle disease virus (NDV); however, serum malondialdehyde and uric acid were increased. All of these changes were attenuated (P < 0.05) by dietary FSE supplementation. At d 42, FSE supplementation improved (P < 0.05) the apparent digestibility of DM and CP, relative weights of bursa, SOD activity, and antibody titers to NDV, which were impaired by CS administration. Interactions (P < 0.05) were noted between CS and FSE for ADG and feed conversion ratio in the finisher phase and overall, as well as total antioxidant capacity, SOD activity, uric acid, and antibody titers to NDV at d 21, as well as relative weights of thymus at d 42. In conclusion, dietary FSE supplementation enhanced nutrient digestibility and performance of broiler possibly by reducing oxidative stress and immune depression challenged by CS.
Assuntos
Galinhas/fisiologia , Forsythia/química , Sistema Imunitário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ração Animal , Animais , Anticorpos Antivirais/sangue , Análise Química do Sangue/veterinária , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Corticosterona/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Inibidores do Crescimento/farmacologia , Masculino , Vírus da Doença de Newcastle/imunologiaRESUMO
A 42-d experiment was conducted with 276 Arbor Acres broilers (1 d of age, weighing 41.1 ± 1.5 g) to determine the effects of Forsythia suspensa extract (FSE) and berberine (BE) on growth performance, immunity, antioxidant activities, and intestinal microbiota stocked at high stocking density (28 kg of BW/m(2) as the normal density, 46 kg of BW/m(2) as the high density). The feeding program consisted of a starter diet from d 1 to 21 of age and a finisher diet from d 22 to 42. Dietary treatments included (1) negative control group (NC), stocked at high density; (2) positive control group (PC), stocked at normal density; (3) FSE, NC + 100 mg/kg of FSE; (4) BE, NC + 100 mg/kg of BE; and (5) FSE + BE, NC + 100 mg/kg of FSE + 100 mg/kg of BE. Birds had free access to diets and water. Body weight and feed intake were measured at d 21 and 42. Blood, spleen and bursa, and intestinal contents were collected at d 42 for analysis. The results showed that growth performance did not differ among treatments in the starter period; however, in the finisher and overall periods, birds in FSE + BE, FSE, BE, and PC had greater final BW, ADG, and ADFI than the birds in NC (P < 0.05). The birds in FSE + BE, FSE, BE, and PC had greater bursa weight, bursa weight/BW ratio, serum total antioxidant capacity, and superoxide dismutase activity than birds in NC (P < 0.05). The FSE + BE, FSE, and BE birds had lower serum malondialdehyde level than NC birds (P < 0.05). The FSE + BE, FSE, BE, and PC birds had lower counts of Escherichia coli but greater Lactobacillus in the cecum than that of NC birds (P < 0.05). Dietary supplementation with FSE, BE, or both can improve the growth performance possibly by enhancing immunity, reducing oxidative stress, and promoting intestinal colonization by healthy microbiota of broilers under high stocking density.
Assuntos
Antioxidantes/metabolismo , Berberina/farmacologia , Galinhas/crescimento & desenvolvimento , Forsythia/química , Intestinos/microbiologia , Extratos Vegetais/farmacologia , Animais , Bolsa de Fabricius/anatomia & histologia , Bolsa de Fabricius/efeitos dos fármacos , Galinhas/imunologia , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Baço/anatomia & histologia , Baço/efeitos dos fármacos , Estresse FisiológicoRESUMO
Two experiments were conducted to evaluate the effect of supplementing a corn-soybean meal-based diet with an enzyme complex containing amylase, protease and xylanase on the performance, intestinal health, apparent ileal digestibility of amino acids and nutrient digestibility of weaned pigs. In Exp. 1, 108 piglets weaned at 28 d of age were fed one of three diets containing 0 (control), 100, or 150 ppm enzyme complex for 4 wks, based on a two-phase feeding program namely 1 to 7 d (phase 1) and 8 to 28 d (phase 2). At the end of the experiment, six pigs from the control group and the group supplemented with 150 ppm enzyme complex were chosen to collect digesta samples from intestine to measure viscosity and pH in the stomach, ileum, and cecum, as well as volatile fatty acid concentrations and composition of the microflora in the cecum and colon. There were linear increases (p<0.01) in weight gain, gain: feed ratio and digestibility of gross energy with the increasing dose rate of enzyme supplementation during the whole experiment. Supplementation with enzyme complex increased the digesta viscosity in the stomach (p<0.05) and significantly increased (p<0.01) the concentrations of acetic, propionic and butyric acid in the cecum and colon. Enzyme supplementation also significantly increased the population of Lactobacilli (p<0.01) in the cecum and decreased the population of E. coli (p<0.05) in the colon. In Exp. 2, six crossbred barrows (initial body weight: 18.26±1.21 kg), fitted with a simple T-cannula at the distal ileum, were assigned to three dietary treatments according to a replicated 3×3 Latin Square design. The experimental diets were the same as the diets used in phase 2 in Exp. 1. Apparent ileal digestibility of isoleucine (p<0.01), valine (p<0.05) and aspartic acid (p<0.05) linearly increased with the increasing dose rate of enzyme supplementation. In conclusion, supplementation of the diet with an enzyme complex containing amylase, protease and xylanase improved piglet performance. This is likely a result of improvement in nutrient digestibility, volatile fatty acid concentrations and bacteria ratio in the large intestine.
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Three experiments were conducted to evaluate the ME value, standardized ileal digestibility (SID) of amino acids (AA) of fish meal, and the effects of single cell protein (Prosin and Protide) replacing fish meal in diet on growth performance, nutrient digestibility and intestinal morphology in weaned piglets. In Exp. 1, twenty-four barrows with initial BW of 30.8±2.6 kg were allotted to one of four dietary treatments. Diet 1 contained corn as the only energy source. The other three diets replaced 20% of the corn in diet 1 with one of the three protein feeds (fish meal, Prosin and Protide), and the DE and ME contents were determined by difference. In Exp. 2, eight barrows (initial BW of 25.6±3.2 kg) were fitted with ileal T-cannulas and allotted to a replicated 4×4 Latin square design. Three cornstarch-based diets were formulated using each of the protein feeds as the sole source of AA. A nitrogen-free diet was also formulated to measure endogenous losses of AA. In Exp. 3, one hundred and eighty piglets (initial BW of 7.95±1.59 kg) weaned at 28±2 d were blocked by weight and assigned to one of five treatments for a 28-d growth performance study, each treatment was fed to six pens with six pigs (three barrows and three gilts) per pen. The five treatments consisted of the control group (CON), which was a corn-soybean meal diet containing 5% fish meal, and the other four treatments, which replaced a set amount of fish meal with either Prosin (2.5% or 5%) or Protide (2.5% or 5%). The diets were formulated to provide same nutrient levels. The results showed that on a DM basis, both of the DE and ME contents were lower in Prosin and Protide than that of fish meal (p<0.05). The SID of CP and all essential AA were greater in fish meal than in Prosin and Protide (p<0.05). The pigs fed CON diet had greater weight gain and lower feed conversion rate (FCR) than pigs fed 5% Prosin and 5% Protide diets (p<0.05). The digestibility of CP was greater in pigs fed CON, 2.5% Prosin and 2.5% Protide diets than the pigs fed 5% Prosin and 5% Protide diets (p<0.05). Villus height in jejunum and ileum, and villus height to crypt depth ratio in the jejunum were higher (p<0.05) in pigs fed CON, 2.5% Prosin and 2.5% Protide diets compared with the 5% Prosin and 5% Protide diets. Pigs fed CON diet had greater villus height to crypt depth ratio in the ileum than the pigs fed 5% Prosin and 5% Protide diets (p<0.05). In conclusion, although Prosin and Protide contained lower ME content and SID of AA than fish meal, Prosin and Protide replacing 50% of fish meal in diet with identical nutrient levels could obtain similar performance, nutrient digestibility and intestinal morphology in weaned pigs.
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Although two kinds of Liobagrus marginatoides should belong to the same species according to the taxonomy of fish morphology, the results of cytogenetic analysis showed they are two different races.
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Peixes-Gato/classificação , Animais , Peixes-Gato/genética , China , Cromossomos/genética , Feminino , Cariotipagem , Masculino , RiosRESUMO
The aim of this study was to remove ammonium from aqueous solution and recycle ammonium. Ammonium removal from aqueous solution by natural and pretreated zeolites, breakthrough curve, chemical regeneration of pretreated zeolite, ammonium removal from regeneration solution by chemical precipitation and NH(4) (+) adsorption isotherms were investigated by conducting a series of batch and continuous experiments in this study. Morphologies and structures of zeolites were analyzed by Surface Area and Pore Size analysis, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) spectroscopy. The NH(4) (+)-N removal efficiencies by natural and NaCl-treated zeolite were 30.73% and 85.55% respectively at an initial concentration of 100 mg/L. Breakthrough and exhaustion capacities for adsorption of ammonium ions were 3.36 and 4.26 mg /g (NH(4) (+)-N/zeolite), respectively. After chemical regeneration, NH(4) (+)-N removal efficiency by NaCl-treated zeolite only reduced 9.95% than previously. NH(4) (+)-N concentration of the regeneration solution was reduced from 460 to 74.55 mg/L by chemical precipitation. The Freundlich isotherm provided a slightly more consistent fit to the experimental data of ammonium adsorption on NaCl-treated zeolite than Langmuir. Based on the results, it was concluded that the objective of this study had been well achieved.