A prospective multicentre controlled study of Gaoweikang (Chinese multiherb extract-based tincture) used in high-risk HPV infections.

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

[A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis].

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (ß=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (ß=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (ß=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (ß=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (ß=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (ß=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (ß=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (ß=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

[Analysis and significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term NAs antiviral therapy in patients with hepatitis B virus cirrhosis].

Objective: To analyze the significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term nucleos(t)ide analogues (NAs) antiviral therapy in patients with hepatitis B virus cirrhosis. Methods: 97 cases with hepatitis B virus cirrhosis treated with NAs antiviral therapy for at least 3 years between May 2018 to July 2019 were selected. High-sensitivity HBV DNA (<20 IU/ml), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), HBsAg, HBeAg and HBV RNA at least twice every 6 months were detected. According to Child-Pugh classification, HBeAg, HBsAg level, and HBV RNA level intergroup comparison was performed. Rank sum test, χ2 test and linear regression analysis were performed on the data. Results: Compared with the HBV RNA level of child-Pugh class A patients, the HBV RNA level of Child-Pugh class B+C patients were significantly higher [4.1 (0,4.9) log10 copies/ml and 2.0 (0,3.5) log10 copies/ml], and the difference was statistically significant (Z=2.370, P<0.05). According to different HBeAg levels, they were divided into HBeAg positive and negative group, and the quantitative comparison of HBV RNA levels between the two groups were 2.0 (0, 4.5) log10 copies/ml and 1.0 (1.0, 2.0) log10 copies/ml, respectively, and the difference was statistically significant (Z=3.233, P<0.05). According to different HBsAg levels, they were divided into three groups: HBsAg≤100 IU/ml, 100

Effects of a combination of fibrolytic and amylolytic enzymes on ruminal enzyme activities, bacterial diversity, blood profile and milk production in dairy cows.

We hypothesised that adding a combination of fibrolytic and amylolytic enzymes to the diet of early-lactation dairy cows would improve rumen enzyme activity and bacterial diversity, promote energy metabolism, and benefit milk production in cows. Twenty multiparous early-lactation (90 ±â€¯5 d) Holstein cows with similar body conditions were randomly allocated to control (CON, n = 10) and experimental (EXP, n = 10) groups in a completely randomised single-factor design. The CON was fed only a basal total mixed ration diet, and the diet of the EXP was supplemented with a combination of fibrolytic and amylolytic enzymes at 70 g/cow/d (cellulase 3 500 CU/g, xylanase 2 000 XU/g, ß-glucanase 17 500 GU/g, and amylase 37 000 AU/g). The experiment lasted 28 days, with 21 days for adaptation and 7 days for sampling. Enzyme addition increased the activity levels of α-amylase and xylanase, and the ammonia-N concentration (P < 0.05) tended to increase the activity of ß-glucanase (P = 0.08) in rumen fluid. However, there was no significant difference in the rumen bacterial richness and diversity, phylum (richness > 0.1%) or genus (richness > 1%) composition between the CON and EXP groups (P > 0.05). A tendency of difference was found between CON and EXP (R = 0.22, P = 0.098) in principal component analysis. Ten genera showed different abundances across the CON and EXP groups (linear discriminant analysis effect size, linear discriminant analysis > 2). EXP increased the ratio of albumin to globulin and the concentrations of total cholesterol and low-density lipoprotein cholesterol (P < 0.05) and tended to increase triglycerides (P = 0.09) in blood. Milk yield, 3.5% fat-corrected milk yield and energy-corrected milk yield increased with enzyme supplementation (P < 0.05). The production levels of milk fat and lactose increased, but the percentage of solids, not fat and protein, decreased in EXP (P < 0.05). Although the DM intake was not affected, the feed efficiency tended to increase (P = 0.07) in EXP. In conclusion, dietary supplementation with a mixture of fibrolytic and amylolytic enzymes on multiparous early-lactation dairy cows increased α-amylase and xylanase activity levels in rumen fluid, enhanced milk performance and tended to improve the feed efficiency in cows.

Mapping the twist-angle disorder and Landau levels in magic-angle graphene.

The recently discovered flat electronic bands and strongly correlated and superconducting phases in magic-angle twisted bilayer graphene (MATBG)1,2 crucially depend on the interlayer twist angle, θ. Although control of the global θ with a precision of about 0.1 degrees has been demonstrated1-7, little information is available on the distribution of the local twist angles. Here we use a nanoscale on-tip scanning superconducting quantum interference device (SQUID-on-tip)8 to obtain tomographic images of the Landau levels in the quantum Hall state9 and to map the local θ variations in hexagonal boron nitride (hBN)-encapsulated MATBG devices with relative precision better than 0.002 degrees and a spatial resolution of a few moiré periods. We find a correlation between the degree of θ disorder and the quality of the MATBG transport characteristics and show that even state-of-the-art devices-which exhibit correlated states, Landau fans and superconductivity-display considerable local variation in θ of up to 0.1 degrees, exhibiting substantial gradients and networks of jumps, and may contain areas with no local MATBG behaviour. We observe that the correlated states in MATBG are particularly fragile with respect to the twist-angle disorder. We also show that the gradients of θ generate large gate-tunable in-plane electric fields, unscreened even in the metallic regions, which profoundly alter the quantum Hall state by forming edge channels in the bulk of the sample and may affect the phase diagram of the correlated and superconducting states. We thus establish the importance of θ disorder as an unconventional type of disorder enabling the use of twist-angle gradients for bandstructure engineering, for realization of correlated phenomena and for gate-tunable built-in planar electric fields for device applications.

[Retrospective cohort study on subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy in the treatment of senile slow transit constipation].

Objective: To investigate the clinical efficacy of laparoscopic subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy (SCBCAC) in the treatment of senile slow transit constipation. Methods: A retrospective cohort study was performed. Clinical data of 30 colonic slow transit constipation patients aged ≥70 years old undergoing laparoscopic SCBCAC from July 2012 to October 2016 (bypass plus colostomy group), and 28 patients undergoing laparoscopic subtotal colonic bypass with antiperistaltic cecoproctostomy (SCBAC) from February 2009 to June 2012 (bypass group) at our institute were collected. Efficacy was compared between the two procedures. Inclusion criteria: (1) meeting the Rome III diagnosis criteria for constipation; (2) confirmed diagnosis of slow transit constipation; (3) age ≥ 70 years old; (4) receiving non-surgical treatment for more than 5 years, and Wexner constipation score > 15; (5) follow-up for more than 2 years. Those with psychiatric symptoms or previous psychiatric history, obvious signs of outlet obstructive constipation, organic diseases of the colon and life-threatening cardiovascular diseases or cancer were excluded. In the bypass plus colostomy group, laparoscopy was performed via five trocars. The ileocecal junction and the ascending colon were mobilized and the ileocecal junction was pulled down to the pelvic inlet. The ascending colon was transected and the appendix was excised. The lateral peritoneum of the sigmoid colon and the rectal mesentery were dissected and the upper rectum was transected. The avil of a circular stapler was placed in the bottom of the cecum. The shaft of the stapler was placed in the rectum via the anal canal to complete end-to-side anastomosis (end rectum to lateral cecum). The end of the rectal-sigmoid colon was used for colostomy via an extraperitoneal approach to complete the operation. The following efficacy indexes were collected before surgery and 3, 6, 12, and 24 months after surgery: the number of daily bowel movements, the Wexner incontinence scale (WIS, 0-20, the lower the better), the Wexner constipation scale (WCS, 0-30, the lower the better), the gastrointestinal quality of life index (GIQLI, 0-144, the higher score, the better), abdominal pain intensity indicated by the numerical rating scale (NRS, 0-10, the lower score, the better), and the abdominal bloating score (ABS, 0-4, the lower score, the better). The complications defined as Clavien-Dindo class II or above were observed and recorded. Results: No significant differences in preoperative WCS, WIS, GIQLI, NRS, and ABS were observed between bypass plus colostomy group and bypass group (all P>0.05). All the patients successfully underwent laparoscopic surgery and no patient in either group experienced postoperative fecal incontinence. WCS and GIQLI were significantly improved (all P<0.001) at 3, 6, 12, and 24 months after surgery in both groups. At 12 months after surgery, the number of bowel movements was significantly less in bypass plus colostomy group than that in bypass group [(2.4±0.7) times vs. (3.4±1.2) times, t=4.048, P<0.001]. At 3, 6, 12 and 24 months after surgery, the improvement of GIQLI in bypass plus colostomy group was significantly better than that in bypass group (all P<0.001). At 24 months after surgery, GIQLI in bypass plus colostomy group and bypass group was 122.3±5.3 and 92.8±16.6, respectively, with a significant difference (t=9.276, P<0.001). At 12 and 24 months after surgery, NRS in bypass plus colostomy group was significantly better than that in bypass group (both P<0.001). At 24 months after surgery, NRS in bypass plus colostomy group was 0.9±0.7, while that in bypass group was 3.7±2.7. There was a significant difference between two groups (t=5.585, P<0.001). At 6, 12 and 24 months after surgery, the improvement of ABS in bypass plus colostomy group was also significantly better than that in bypass group. At 24 months after surgery, ABS in bypass plus colostomy group was 0.6±0.6, while that in bypass group was 2.5±1.0, with a significant difference between two groups (t=8.797, P<0.001). At 1 year after surgery, barium enema examination was performed in all the patients of both groups. The barium emptying time was (21.2±3.8) hours and (95.8±86.2) hours in bypass plus colostomy group and bypass group respectively. The former group was significantly better than the latter group (t=4.740, P<0.001). Conclusions: Laparoscopic SCBCAC is an effective and safe procedure for the treatment of senile slow transit constipation and can significantly improve prognosis. Its clinical efficacy is better than laparoscopic SCBAC.

Granny Smith apple procyanidin extract upregulates tight junction protein expression and modulates oxidative stress and inflammation in lipopolysaccharide-induced Caco-2 cells.

The present work is undertaken to characterize a Granny Smith apple procyanidin extract (AE) and investigate the beneficial effect of the AE in the intestine in vitro. Each AE was characterized via LC-ESI-MS. Caco-2 cells were used to study the preventive actions of the AE against the downregulation of tight junction protein expression, oxidative stress and inflammation induced by lipopolysaccharides (LPS). Phenolic compounds present in the AE, including chlorogenic acid, catechin, epicatechin, proanthocyanidin dimers, and proanthocyanidin trimers, were characterized. The expression of the tight junction protein, including occludin and zona occludens (ZO)-1, increased significantly in LPS + AE treated Caco-2 cells, compared to LPS induced Caco-2 cells. Proanthocyanidin dimers had the most potent effect on increasing tight junction protein expression. The addition of LPS to Caco-2 cells induced oxidative stress and inflammation. However, incubation with proanthocyanidin dimers prevented LPS-mediated oxidative stress, including the increase of SOD, HO-1, CAT, and GSH-Px mRNA expression, and counteracted LPS-mediated inflammation as evidenced by the down-regulation of inflammatory markers (NF-κß, IL-6, and TNF-α mRNA expression). Our findings provide evidence that AE could upregulate tight junction protein expression, probably acting via the reduction of oxidative stress and inflammation.

Effects of dietary leucine and phenylalanine on pancreas development, enzyme activity, and relative gene expression in milk-fed Holstein dairy calves.

This study aimed to investigate the effect of dietary supplementation with leucine and phenylalanine on pancreas development, enzyme activity, and related gene expression in male Holstein calves. Twenty male Holstein calves [1 d of age, 38 ± 3 kg of body weight (BW)] were randomly assigned to 1 of the following 4 treatment groups with 5 calves in each group: control, leucine supplementation (1.435 g/L of milk), phenylalanine supplementation (0.725 g/L of milk), and leucine and phenylalanine (1.435 + 0.725 g/L of milk). The diets were made isonitrogenous with the inclusion of alanine in each respective treatment. The feeding trial lasted for 8 wk, including 1 wk for adaption and 7 wk for the feeding experiment. Leucine tended to increase the concentration of total pancreatic protein (mg/kg of BW). Phenylalanine increased the concentrations of plasma insulin, cholecystokinin, and pancreatic DNA (mg/g) and the expression of trypsin gene but decreased the pancreatic protein:DNA ratio and tended to decrease the pancreas weight (g/kg of BW). No differences were observed in total pancreatic DNA (mg/pancreas and mg/kg of BW), pancreatic protein (mg/pancreas), or activities of α-amylase, trypsin, and lipase. The relative expression levels of the genes encoding α-amylase and lipase did not differ among the 4 groups. The supplementation of both leucine and phenylalanine showed an interaction on the pancreas weight (g and g/kg of BW) and a tendency of an interaction on the pancreatic protein concentration (mg/g of pancreas and mg/kg of BW) and the plasma glucose concentration. Leucine tended to increase the size of the pancreatic cells, whereas phenylalanine tended to increase the number of pancreatic cells. However, neither AA affected the activities of the pancreatic enzymes of the calves. These results indicate that leucine and phenylalanine supplementation in milk-fed Holstein calves differentially affect pancreatic growth and development.

Polyphenols in Eucalyptus leaves improved the egg and meat qualities and protected against ethanol-induced oxidative damage in laying hens.

Polyphenols in Eucalyptus leaves (PE) were value resources due to various pharmacological activities, but data on the effect on laying hens are very scare. This study was conducted to determine the effect of PE on the laying performance, egg traits, meat quality, antioxidant status and liver tissues of laying hens. One hundred and twenty 256-day-old Yueqinhuang laying hens were randomly assigned to four treatment groups (different levels of PE at 0, 0.5, 0.8 and 1.2 g/kg diet) for 63 days with 15 replicates per group. Addition of 0.8 g/kg PE not only improved the egg trait by increasing the eggshell thickness and decreasing MDA production and cholesterol content in the egg yolk, but also significantly enhanced meat quality of hens, as suggested by the increase pH45 min (p < .01) and a* value, and decrease drip loss rate (p < .01). Meanwhile, under acute ethanol-induced oxidative damage condition, supplementation of 0.8 g/kg PE enhanced the serum antioxidant status by increasing enzymatic activities (GSH-PX, T-SOD, T-AOC), inhibited oxidative damage and provided protective effect to liver tissue. In conclusion, addition of 0.8 g/kg PE not only improved the egg traits and meat quality without obvious adverse effects, but also increased the serum antioxidant status of the hens and protected their liver tissue from ethanol-induced oxidative damage. This study indicated that PE could be utilized as an effective feed additive for laying hens to improve health performance and egg traits.

[Predictive and Prognostic significance of high-sensitivity modified Glasgow Prognostic Score (HS-mGPS) in advanced gastric cancer patients treated with neoadjuvant chemotherapy].

Objective: To study the predictive and prognostic significance of high-sensitivity modified Glasgow Prognostic Score (HS-mGPS) on the effect of neoadjuvant chemotherapy for advanced gastric cancer. Methods: 117 patients with advanced gastric cancer received neoadjuvant chemotherapy with SOX (oxaliplatin+ S1) or mFOLFOX 6(oxaliplatin+ CF+ 5-FU) regimen. HS-mGPS was calculated according to blood C-reactive protein (CRP) concentration and serum albumin (ALB) level. The correlation between HS-mGPS and clinicopathological characteristics was determined and the predictors of survival were analyzed. Results: 117 patients with stage ⅡB (43 cases), stage Ⅲ (60), and stage Ⅳ (14) received preoperative neoadjuvant chemotherapy. The overall response rate of neoadjuvant chemotherapy was 61.5%(72/117), and the tumor control rate was 88.0% (103/117), with a pathological response rate of 91.5% (107/117). The R0 resection rate was 81.2% (95/117). The median disease-free survival (DFS) was 21.0 (95% CI 6.4-35.6) months. The median overall survival (OS) was 39.0 (95% CI 21.4-56.6) months. Higher HS-mGPS was associated with higher T stage, local lymph-node metastasis, distant metastasis, lower chemotherapy overall response rate and lower pathological response rate (all P<0.05). The univariate analysis and multivariate analysis showed that higher HS-mGPS, presence of local lymph-node metastasis and non R0 resection were associated with poorer DFS and OS (P<0.05). Conclusion: HS-mGPS can be used to predict the benefits of neoadjuvant chemotherapy and as an independent prognostic factor for survival in patients with advanced gastric cancer.

Effects of exogenous phytase and xylanase, individually or in combination, and pelleting on nutrient digestibility, available energy content of wheat and performance of growing pigs fed wheat-based diets.

OBJECTIVE: Two experiments were conducted to determine the effects of adding exogenous phytase and xylanase, individually or in combination, as well as pelleting on nutrient digestibility, available energy content of wheat and the performance of growing pigs fed wheat-based diets. METHODS: In Experiment 1, forty-eight barrows with an initial body weight of 35.9±0.6 kg were randomly assigned to a 2×4 factorial experiment with the main effects being feed form (pellet vs meal) and enzyme supplementation (none, 10,000 U/kg phytase, 4,000 U/kg xylanase or 10,000 U/kg phytase plus 4,000 U/kg xylanase). The basal diet contained 97.8% wheat. Pigs were placed in metabolic cages for a 7-d adaptation period followed by a 5-d total collection of feces and urine. Nutrient digestibility and available energy content were determined. Experiment 2 was conducted to evaluate the effects of pelleting and enzymes on performance of wheat for growing pigs. In this experiment, 180 growing pigs (35.2±9.0 kg BW) were allocated to 1 of 6 treatments according to a 2×3 factorial treatment arrangement with the main effects being feed form (meal vs pellet) and enzyme supplementation (0, 2,500 or 5,000 U/kg xylanase). RESULTS: In Experiment 1, there were no interactions between feed form and enzyme supplementation. Pelleting reduced the digestibility of acid detergent fiber (ADF) by 6.4 percentage units (p<0.01), increased the digestibility of energy by 0.6 percentage units (p<0.05), and tended to improve the digestibility of crude protein by 0.5 percentage units (p = 0.07) compared with diets in mash form. The addition of phytase improved the digestibility of phosphorus (p<0.01) and calcium (p<0.01) by 6.9 and 7.6 percentage units respectively compared with control group. Adding xylanase tended to increase the digestibility of crude protein by 1.0 percentage units (p = 0.09) and increased the digestibility of neutral detergent fiber (NDF) (p<0.01) compared with control group. Supplementation of the xylanase-phytase combination improved the digestibility of phosphorus (p<0.01) but impaired NDF digestibility (p<0.05) compared with adding xylanase alone. In Experiment 2, adding xylanase increased average daily gain (p<0.01) and linearly improved the feed:gain ratio (p<0.01) compared with control group. CONCLUSION: Pelleting improved energy digestibility but decreased ADF digestibility. Adding xylanase increased crude protein digestibility and pig performance. Phytase increased the apparent total tract digestibility of phosphorus and calcium. The combination of phytase-xylanase supplementation impaired the effects of xylanase on NDF digestibility.

Effect of total peony glucoside pretreatment on NF-κB and ICAM-1 expression in myocardial tissue of rat with myocardial ischemia-reperfusion injury.

Early recovery of myocardial perfusion is beneficial for myocardial ischemia. However, ischemia-reperfusion (I/R) may exacerbate myocardial injury. Research shows that total peony glucoside (TPG) can inhibit ischemic myocardial cell apoptosis. However, whether it can ameliorate I/R injury remains poorly understood. This study explored the effect of TPG pretreatment on I/R, through nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) expressions in I/R-affected myocardium. Healthy 7-week-old male Sprague Dawley rats were randomly categorized into sham operation (A), modeling (B), and 100, 200, and 400 mg/kg TPG pretreatment groups (C, D, and E, respectively), with 20 rats in each group. I/R rat models were designed by ligating left anterior descending coronary artery for 30 min to induce ischemia and for 120 min to induce reperfusion. Serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels were measured using enzyme linked immunosorbent assay. NF-κB and ICAM-1 mRNA and protein expressions were detected through RT-PCR and western blot analysis, respectively. Compared to group A, serum IL-6 and IL-8 levels of group B elevated significantly (P < 0.05), whereas NF-κB and ICAM-1 mRNA and protein expressions increased in the myocardium (P < 0.05). Serum IL-6 and IL-8 levels, and NF-κB and ICAM-1 mRNA and protein expressions, in myocardium of TPG groups reduced in a dose-dependent manner. Therefore, TPG pretreatment could alleviate myocardium reperfusion injury in I/R rat models by reducing NF-κB and ICAM-1 mRNA and protein expressions and cytokine secretions. This mechanism could be associated with the inhibition of NF-κB activation and downregulation of ICAM-1 expression.

Dietary zinc may attenuate heat-induced testicular oxidative stress in mice via up-regulation of Cu-Zn SOD.

Zinc (Zn) is important for male mammalian reproduction. In this study, we sought to clarify the role of Zn in heat-induced testicular damage in mice. Eighteen mice were divided into either control (con), heat (heat) and heat plus Zn (H+Zn) treatment groups, and fed diets containing 60 (con and heat groups) or 300 (H+Zn group) mg/kg Zn sulfate for one month. Mice in the con group were then maintained at 25°C, while mice in heat and H+Zn groups were exposed to 40°C for 2 h daily, for eight days. Mouse testes and serum from each animal were analyzed. Zinc levels in serum and testes were positively correlated to Zn feed concentrations. Mice in the heat group had higher testes index than those in the other two groups (7.22 ± 0.75, heat; 4.92 ± 0.20, con; 4.80 ± 0.30 mg/g, H+Zn; P < 0.05). Testicular antioxidant status showed malondialdehyde levels in heat group mice were increased compared to control mice (2.34 ± 0.15 versus 1.55 ± 0.23 nmol/mg protein; P < 0.05), and Cu-Zn superoxide dismutase (SOD) level differed between heat and H+Zn groups (14.04 ± 0.74 versus 18.27 ± 1.53 U/mg protein; P < 0.05). Testicular Cu-Zn SOD protein expression levels were significantly lower in the heat than in the control group (0.30 ± 0.11 versus 1.22 ± 0.13; P < 0.05). These results suggest that dietary Zn may elevate the activity and protein concentration of Cu-Zn SOD, to attenuate testicular oxidative stress induced by heat exposure.

Effects of zinc sulfate pretreatment on heat tolerance of Bama miniature pig under high ambient temperature.

The aim of this study was to evaluate the heat tolerance of Bama miniature pigs under high ambient temperature (40°C) and Zn interactive functions during heat treatment (HT). Bama miniature pigs (male; n = 24; 6-mo old; BW = 10.79 ± 0.06 kg) were randomly allotted to 4 groups and were fed a basal diet or the basal diet supplemented with 1,500 mg of Zn (ZnSO4·H2O)/kg diet for 38 d. At 7 mo of age (d 30), the thermal neutral (TN) groups remained at 25°C, whereas the HT groups were exposed to ambient temperature at 40°C for 5 h daily for 8 consecutive days. Pigs in 4 groups were sacrificed on d 38. Individual rectal temperatures, skin temperatures, and breathing rates were recorded at 3 h after the onset of HT and the blood samples were collected immediately after HT on d 30, 34, and 38. Pigs fed diets with or without Zn doubled their breathing rates (P < 0.05) and increased body surface, scrotal, and rectal temperatures during HT on d 30, 34, and 38, respectively. Zinc supplementation increased BW gain (BWG; P < 0.05) during 38-d experiment period, and HT decreased BWG only from d 30 to 34 (P < 0.05). Heat treatment increased serum testosterone on d 30 (P < 0.05). Zinc supplementation decreased the heat-induced increase of testosterone in HT on d 30 and 34 (P < 0.05). The relative weight of liver increased in HT groups (P < 0.05). Zinc supplementation decreased the relative weights of spleen (P < 0.05) and testis (P < 0.01). The values of abnormal lymphocyte count and large unstained cell count declined approximately 5 times in groups of Zn supplementation, whereas Zn supplementation increased the values of red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin. Zinc concentrations increased in serum, liver, kidney, epididymis, longissimus, hair, and feces in groups fed with Zn (P < 0.01). However, additional Zn decreased Zn concentrations in lung, spleen, and testis (P < 0.01). Moreover, HT decreased serum Zn concentrations (P < 0.01). In conclusion, Zn supplementation could be used to alleviate the decline of serum Zn during periods of high ambient temperatures. However, pretreated supplementation with pharmacological Zn did not promote heat tolerance but impacted the erythropoiesis, immunity, and reproductive organ development in Bama miniature pigs.

Glucose- and Triglyceride-lowering Dietary Penta-O-galloyl-α-D-Glucose Reduces Expression of PPARγ and C/EBPα, Induces p21-Mediated G1 Phase Cell Cycle Arrest, and Inhibits Adipogenesis in 3T3-L1 Preadipocytes.

Plant polyphenols, such as hydrolysable tannins, are present in the human diet and known to exhibit anti-diabetic and anti-obesity activity. We previously reported that the representative hydrolysable tannin compound α-penta-galloyl-glucose (α-PGG) is a small molecule insulin mimetic that, like insulin, binds to insulin receptor (IR) and activates the IR-Akt-GLUT4 signaling pathway to trigger glucose transport and reduce blood glucose levels in db/db and ob/ob diabetic mice. However, its effects on adipogenesis and lipid metabolism were not known. In this study, high fat diet (HFD)-induced diabetic and obese mice were treated with α-PGG to determine its effects on blood glucose and triglycerides. 3T3-L1 preadipocytes were used as a cell model for identifying the anti-adipogenic activity of α-PGG at molecular and cellular levels as a first step in elucidating the mechanism of action of the compound. In vivo, oral administration of α-PGG significantly reduced levels of blood glucose, triglyceride, and insulin in HFD-induced diabetic/obese mice (P<0.05). In vitro, α-PGG inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes. α-PGG suppressed the expression of positive adipogenic factors PPARγ C/EBPα and mTOR and augmented the negative adipogenic factor Pref-1. Furthermore, α-PGG induced upregulation of p21 and G1 phase cell cycle arrest. In contrast, adipogenic signaling pathways mediated by insulin, the cAMP response element binding protein (CREB) and glucocorticoid receptor (GR), were not inhibited. RNAi knockdown of p21 led to a 4-fold increase in triglyceride level in 3T3-L1 preadipocytes treated with MDI and α-PGG compared to regular preadipocytes. These results indicate, for the first time, that α-PGG is blood triglyceride- and glucose-lowering in HFD-induced obese and diabetic mice. It selectively inhibited some but not all major adipogenic pathways as well as the mTOR-p21-mediated cell cycle regulatory pathway. It is very likely that these apparently diverse but coordinated activities together inhibited adipogenesis. These results expand our knowledge on how PGG works in adipocytes and further confirm that α-PGG functions as an orally-deliverable natural insulin mimetic with adipogenetic modulatory functions.

An ex vivo study of arrested primary teeth caries with silver diamine fluoride therapy.

OBJECTIVES: This ex vivo study compared the physico-chemical structural differences between primary carious teeth biannually treated with silver diamine fluoride (SDF) and carious teeth without such treatment. METHOD: Twelve carious primary upper-central incisors were collected from 6-year-old children. Six teeth had arrested caries after 24-month biannual SDF applications and 6 had active caries when there was no topical fluoride treatment. The mineral density, elemental contents, surface morphology, and crystal characteristics were assessed by micro-computed tomography (micro-CT), energy-dispersive X-ray spectrometry (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). RESULTS: Micro-CT examination revealed a superficial opaque band approximately 150µm on the arrested cavitated dentinal lesion. This band was limited in the active carious lesion. EDX examination detected a higher intensity of calcium and phosphate of 150µm in the surface zone than in the inner zone, but this zone was restricted in the active cavitated dentinal lesion. SEM examination indicated that the collagens were protected from being exposed in the arrested cavitated dentinal lesion, but were exposed in the active cavitated dentinal lesion. TEM examination suggested that remineralised hydroxyapatites were well aligned in the arrested cavitated dentinal lesion, while those in the active cavitated dentinal lesion indicated a random apatite arrangement. CONCLUSIONS: A highly remineralised zone rich in calcium and phosphate was found on the arrested cavitated dentinal lesion of primary teeth with an SDF application. The collagens were protected from being exposed in the arrested cavitated dentinal lesion. CLINICAL SIGNIFICANCE: Clinical SDF application positively influences dentine remineralisation.

Autophagy facilitates the sorafenib resistance of hepatocellular carcinoma cells / La autofagia facilita la resistencia al sorafenib de las células del carcinoma hepatocelular

Liver cancer is the second most frequent cause of cancer death in men and the sixth leading cause of cancer death in women. Hepatocellular carcinoma (HCC) represents the major subtype in liver cancer and its five-year survival rate remains very poor. Sorafenib, a molecular targeted therapeutic agent, was the first drug approved for the treatment of patients with HCC. However, the clinical response of sorafenib was seriously limited by drug resistance. Autophagy is an evolutionarily conserved mechanism among all eukaryotes. Recently, many studies have indicated that autophagy can be activated as a cellular protective mechanism in many tumour cells. Thus, we hypothesized that autophagy may play an important role in resistance to sorafenib in hepatocellular carcinoma. Although the exact role of autophagy in the sorafenib resistance of HCC is still complex and further studies are needed to be proven, at least it suggests that autophagy may be a new therapeutic target for the sorafenib resistance of HCC.

El cáncer de hígado es la segunda causa de muerte más frecuente por cáncer en los hombres y la sexta causa de muerte por cáncer en las mujeres. El carcinoma hepatocelular (CHC) representa el subtipo principal en el cáncer de hígado, y su tasa de supervivencia de cinco años sigue siendo muy pobre. El sorafenib, un agente terapéutico dirigido selectivamente a moléculas especificas, fue el primer medicamento aprobado para el tratamiento de pacientes con CHC. Sin embargo, la respuesta clínica de sorafenib estaba seriamente limitada por la resistencia al medicamento. La autofagia es un mecanismo evolutivamente conservado entre todos las eucariotas. Recientemente, muchos estudios han indicado que la autofagia puede activarse como mecanismo de protección celular en muchas células tumorales. Por consiguiente, postulamos la hipótesis de que la autofagia puede desempeñar un papel importante en la resistencia del carcinoma hepatocelular al sorafenib. Aunque el papel exacto de la autofagia en la resistencia al sorafenib del CHC es aún complejo y se necesitan estudios adicionales para ser probado, al menos se sugiere que la autofagia puede ser una nueva meta terapéutica frente a la resistencia del sorafenib en el CHC.

Macroscale lateral alignment of semiconductor nanorods into freestanding thin films.

This Communication reports that needle-like supercrystalline colloidal particles can be synthesized through anisotropy-driven self-assembly of 1,12-dodecanediamine-functionalized CdSe/CdS core/shell nanorods. The resulting superparticles exhibit both 1D lamellar and 2D hexagonal supercrystalline orders along directions parallel and perpendicular to the long axis of constituent nanorods, respectively. Our results show that the needle-like superparticles can be unidirectionally aligned through capillary forces on a patterned solid surface and further transferred into macroscopic, uniform, freestanding polymer films, which exhibit strong linear polarized PL with an enhanced polarization ratio, and are useful as energy down-conversion phosphors in polarized LEDs.

Daidzein improves insulin resistance in ovariectomized rats.

OBJECTIVE: To determine whether daidzein improves insulin resistance by modifying weight gain, visceral fat accumulation, blood lipids and serum cytokines levels in ovariectomized Sprague-Dawley rats. MATERIALS AND METHODS: Twenty-eight 12-week-old female rats were divided into three groups: the sham-operated group (SHAM) (n =10), the ovariectomized group receiving daidzein therapy (DAID) (n =10), and the ovariectomized control group (Control) (n =8). The rats in the DAID group received 50 mg/kg daidzein via gavage daily. Weight and food intake were recorded every 2 weeks. All of the animals were euthanized 12 weeks after ovariectomy, after which their fasting insulin, glucose, blood lipids, estradiol, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), adiponectin and leptin levels were measured. RESULTS: After 12 weeks, the ovariectomized rats demonstrated an increase in their body weight and visceral fat; compared to the SHAM rats, the ovariectomized rats also experienced a significant increase in their serum IL-6 levels and insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) (p <0.05). Daidzein therapy decreased weight gain, visceral fat, the HOMA-IR index and IL-6 levels that were induced by ovariectomy. Rats which had received daidzein therapy had lower levels of TNF-α, leptin and blood lipids (except for high density lipoprotein cholesterol) than the other two groups. IL-6 levels positively correlated with the HOMA-IR index in all of the rats after adjustment for body weight (r =0.495; p =0.016). CONCLUSION: We conclude that daidzein can improve insulin resistance induced by ovariectomy by decreasing weight gain, visceral fat accumulation, blood lipids, TNF-α, leptin and IL-6 levels.

Effects of Supplementation of ß-Mannanase in Corn-soybean Meal Diets on Performance and Nutrient Digestibility in Growing Pigs.

A total of 288 crossbred (Duroc×Landrace×Yorkshire) growing pigs were used in two experiments to investigate the effects of adding ß-mannanase to corn-soybean meal-based diets on pig performance and apparent total tract digestibility (ATTD). Both experiments lasted 28 d and were split into two phases namely 1 to 14 days (phase 1) and 15 to 28 days (phase 2). In Exp. 1,144 pigs weighing 23.60±1.59 kg BW were assigned to one of four corn-soybean meal-based diets containing 0, 200, 400 or 600 U/kg ß-mannanase. Increasing the level of ß-mannanase increased weight gain (quadratic effect; p<0.01) and feed efficiency (linear and quadratic effect; p<0.01) during the second phase and the overall experiment. However, performance was unaffected (p>0.05) by treatment during phase 1. Increasing the amount of ß-mannanase in the diet improved (linear and quadratic effect; p<0.05) the ATTD of CP, NDF, ADF, calcium, and phosphorus during both phases. Based on the results of Exp. 1, the optimal supplementation level was determined to be 400 U/kg and this was the level that was applied in Exp. 2. In Exp. 2, 144 pigs weighing 23.50±1.86 kg BW were fed diets containing 0 or 400 U/kg of ß-mannanase and 3,250 or 3,400 kcal/kg digestible energy (DE) in a 2×2 factorial design. ß-Mannanase supplementation increased (p<0.01) weight gain and feed efficiency while the higher energy content increased (p<0.01) feed intake and feed efficiency during both phases and overall. Increased energy content and ß-mannanase supplementation both increased (p<0.05) the ATTD of DM, CP, NDF, ADF, phosphorus, and GE during both phases. There were no significant interactions between energy level and ß-mannanase for any performance or digestibility parameter. In conclusion, the ß-mannanase used in the present experiment improved the performance of growing pigs fed diets based on corn and soybean. The mechanism through which the improvements were obtained appears to be related to improvements in ATTD.