Hair Zinc and Chromium Levels Were Associated with a Reduced Likelihood of Age Related Cognitive Decline in Centenarians and Oldest-Old Adults.

BACKGROUND: Cognitive function has inevitable decline with advancing age in nature, and age-related cognitive decline (ARCD) is of increasing concern to aging population. Scarce study has involved the associations between hair trace elements and ARCD in older adults, especially in centenarians and oldest-old adults. This study was to investigate the associations between hair trace elements and ARCD in centenarians and oldest-old adults. METHODS: Based on the household registration information of centenarians and oldest-old adults provided by the Civil Affairs Department of Hainan Province, China, the investigators conducted a one-to-one household survey among centenarians (≥100 years old) and oldest-old adults (80-99 years old). All 50 centenarians had a median age of 103 years and females accounted for 68.0%. All 73 oldest-old adults aged 80-99 years had a median age of 90 years and females accounted for 82.2%. Basic information were obtained with questionnaire interview, physical examination, biological test and hair collection by pre-trained local doctors and nurses. An inductively coupled plasma mass spectrometer was used to measure hair trace elements. All data in this study comes from China. Age, sex, body mass index, systolic blood pressure, diastolic blood pressure, smoking, drinking, hemoglobin, albumin, fasting blood pressure, zinc, chromium, copper, selenium, iron, manganese, strontium, lead, magnesium, potassium, and barium were simultaneously included in multivariate Logistic regression analysis. One adjusted model was done with all hair trace elements together. RESULTS: Zinc and chromium levels were significantly lower in participants with ARCD than those without ARCD (P < 0.05 for all). Multivariate Logistic regression analysis indicated that zinc [odds ratio (OR): 0.988, 95%confidence interval (95%CI): 0.977-0.999] and chromium (OR: 0.051, 95%CI: 0.004-0.705) were associated with a reduced likelihood of ARCD (P < 0.05 for all). CONCLUSIONS: Hair zinc and chromium levels were associated with a reduced likelihood of ARCD in centenarians and oldest-old adults. Further studies are necessary to verify if zinc and chromium supplementation has the potential to improve cognitive function and prevent ARCD development.

Mercuric-sulphide based metallopharmaceutical formulation as an alternative therapeutic to combat viral and multidrug-resistant (MDR) bacterial infections.

According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5-100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1IIIB, showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal-mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges.

[Near-infrared light therapy ameliorates depression-induced intestinal dysfunction in rats possibly by activating PGC-1α/Nrf2 signaling and increasing hippocampal BDNF expression].

OBJECTIVE: To investigate the effect of near-infrared (NIR) light therapy on depression-induced intestinal dysfunction in rats and explore the possible mechanism. METHODS: Thirty-two male SD rats were randomly divided into control group, model group, low-dose NIR light group and high-dose NIR light group. All the rats except for those in the control group were subjected to chronic restrained stress (CRS) for 4 weeks, and NIR light therapy of the head was administered in the two NIR light groups. The depression- like behaviors, intestinal functions, fecal water content and number of fecal pellets of the rats were evaluated. HE staining was used for detecting histopathological changes in the hippocampus and colon, and hippocampal expressions of BDNF, Nrf2 and PGC-1α were detected with Western blotting. RESULTS: The rats in the CRS model group showed significantly increased immobility time and visceral sensitivity in the behavioral tests, decreased fecal pellets and fecal water content, and lowered expressions of BDNF, Nrf2, and PGC-1α in the hippocampus (P<0.05). Histopathological examination of the CRS rats revealed loosely arranged hippocampal pyramidal cells, obvious neuronal damages, and obvious inflammatory cell infiltration in the colon with irregularly arranged mucosal glands and a high pathological score. High-dose NIR light therapy significantly lowered the immobility time and visceral sensitivity, increased the number of fecal pellets and fecal water content (P<0.05), and enhanced hippocampal expressions of BDNF, Nrf2, and PGC-1α (P<0.05) of the depressive rats. The rats receiving high-dose NIR light therapy also exhibited close arrangement of the hippocampal pyramidal cells with significantly reduced neuronal damage and colonic inflammatory cell infiltration, neatly arranged mucosal glands, and lowered pathological score. CONCLUSION: NIR light therapy can significantly improve depression-like behavior and intestinal function in rats possibly by ameliorating oxidative stress via the PGC-1α/Nrf2 signaling pathway and increasing BDNF level in the hippocampus.

[Efficacy and safety of daratumumab in patients with relapsed/refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) µmol/L, which was significantly higher than that of low dosage group [66 (51, 76) µmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.

[Five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection for Siewert type â ¡ adenocarcinoma of the esophagogastric junction].

Objective: Surgical operation is the main treatment for advanced adenocarcinoma of esophagogastric junction (AEG). Due to its special anatomic location and unique lymph node reflux mode, the surgical treatment of Siewert II AEG is controversial. Lower mediastinal lymph node dissection is one of the most controversial points and a standard technique has not yet been established. This study is aim to explore the safety and feasibility of five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection for Siewert type II AEG. Methods: A descriptive case series study was conducted. The intraoperative and postoperative data of 25 patients with Siewert type II AEG who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph node dissection in Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2019 to April 2021 were retrospectively analyzed. Five-step maneuver was as follows: In the first step, the subcardiac sac was exposed; the right pulmonary ligament lymph nodes and the anterior thoracic paraaortic lymph nodes were dissected cranial to inferior pericardium, left to left edge of thoracic aorta. In the second step, the left diaphragm was opened, and a 12 mm trocar was placed through the 6-7 rib in the left anterior axillary line. The supra-diaphragmatic nodes were dissected through the thoracic operation hole. In the third step, the left inferior pulmonary ligament was severed. The anterior fascia of thoracic aorta was incised to join the anterior space of thoracic aorta formed in the first step and then the lymphatic tissue was dissected upward until the exposure of left inferior pulmonary vein. In the fourth step, the posterior pericardium was denuded retrogradely from ventral side to oral side to the level of left inferior pulmonary vein, right to right pleura, and then the right pulmonary ligament lymph nodes were completely removed. In the fifth step, the esophagus was denuded, and the esophagus was transected 5 cm above the tumor using a linear stapler to complete the dissection of lower thoracic paraesophageal lymph nodes. Results: Operations were successfully completed in 25 patients without conversion, intra-operative complication and perioperative death. Total gastrectomy was performed in 19 cases and proximal gastrectomy in 6 cases. The mean operative time was (268.7±85.6) minutes, the mean estimated blood loss was (90.4±44.2) ml, the mean time of lower mediastinal lymph node dissection was (38.6±10.3) minutes, and the mean harvested number of lower mediastinal lymph node was 5.9±2.9. The length of esophageal invasion was >2 cm in 7 cases and ≤ 2 cm in 18 cases. Eight patients (33.0%) had lower mediastinal lymph node metastasis, including 3 cases with esophageal invasion >2 cm and 5 cases with esophageal invasion ≤ 2 cm. The mean time to postoperative first flatus was (5.5±3.1) days. The average time of postoperative thoracic drainage was (5.9±2.9) days. The mean hospital stay was (9.7±3.1) days. Two patients (8.0%) developed postoperative grade IIIa complications according to the Clavien-Dindo classification, including 1 case of pancreatic fistula and 1 case of pleural effusion, both of whom were cured by puncture drainage. Conclusions: Five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymph nodes dissection for Siewert type II AEG is safe and feasible. Which can ensure sufficient lower mediastinal lymph node dissection to the level of left inferior pulmonary vein.

Artemisia ordosica Polysaccharide Alleviated Lipopolysaccharide-induced Oxidative Stress of Broilers via Nrf2/Keap1 and TLR4/NF-κB Pathway.

Artemisia ordosica is one of the main shrubby perennials belonging to Artemisia species of Asteraceae and could be used in folk Chinese/Mongolian medicine to treat symptoms of various inflammatory ailments. The present study was conducted to investigate the protective effects of dietary Artemisia ordosica polysaccharide (AOP) against lipopolysaccharide (LPS) induced oxidative stress in broilers via Nrf2/Keap1 and TLR4/NF-κB pathway. A total of 192 1-day-old Arbor Acres male broilers were randomly allotted to four treatments with 6 replicates (n = 8): (1) CON group, non-challenged broilers fed basal diet; (2) LPS group, LPS-challenged broilers fed basal diet; (3) AOP group, non-challenged broilers fed basal diet supplemented with 750 mg/kg AOP; (4) LPS+AOP group, LPS-challenged broilers fed basal diet supplemented with 750 mg/kg AOP. The trial included starter phase (d 1-14), stress period Ⅰ (d 15-21), convalescence Ⅰ (d 22-28), stress period Ⅱ (d 29-35) and convalescence Ⅱ (d 36-42). During stress period Ⅰ (on d 15, 17, 19 and 21) and stress period Ⅱ (on d 29, 31, 33 and 35), broilers were injected intra-abdominally either with LPS solution or with an equal amount of sterile saline. The results showed that dietary AOP supplementation alleviated LPS-induced reduction in antioxidant enzyme activity and excessive production of ROS, 8-OHdG and PC in serum of broilers challenged with LPS. Moreover, dietary AOP supplementation alleviated the decrease of T-AOC and activities of SOD, CAT and GPx in liver of broilers challenged with LPS by increasing expression of Nrf2, and inhibiting over-expression of Keap1 both at gene and protein level. Additionally, dietary AOP supplementation decreased the over-production of IL-1ß and IL-6 in liver of broilers challenged by LPS through decreasing mRNA expression of TLR4, MyD88, NF-κB P65, IL-1ß and IL-6, and alleviating the increase of protein expression of TLR4, IKKß, NF-κB P65, IL-1ß, IL-6, and the decrease of protein expression of IkBα. In conclusion, dietary AOP supplementation could alleviate LPS-induced oxidative stress through Nrf2/Keap1 and TLR4/NF-κB pathway.

[Quality assessment of global breast cancer screening guidelines].

Objective: To evaluate the quality of the published breast cancer screening guidelines to provide a reference for domestic studies in the future. Methods: PubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched to identify breast cancer screening guidelines on until August 2020. Two reviewers screened literature and extracted data independently. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREEⅡ) and Reporting Items for Practice Guidelines in Healthcare(RIGHT) tools were used to evaluate the quality of the included guidelines. Results: A total of 15 breast cancer screening guidelines were included, of which seven were published in the United States, with publication years focusing on 2015 to 2019, and 11 guidelines had updated versions. "Rigour of development" (47.0%±22.1%) and "Applicability" (44.0%±15.1%) of AGREEⅡ scored lower than other domains. "Review and quality assurance" (46.7%±39.9%) and "Funding, declaration, and management of interests" (41.7%±24.4%) of RIGHT were reported poorer than others. There were six guidelines recommended and another nine recommended with modifications based on the overall AGREEⅡ score. There were four guidelines with a good level, and another 11 were with a moderate level of RIGHT. The National Comprehensive Cancer Network published the best overall quality guidelines in 2018 (AGREEⅡ: 83.3%, RIGHT: 80.0%) and by the American Cancer Society in 2015 (AGREEⅡ: 83.3%, RIGHT: 85.7%). Conclusion: The quality of breast cancer screening guidelines was predominantly of moderate quality, and greater attention should be paid to the guideline development process and quality control of the guidelines.

[Safety and feasibility of laparoscopic double-flap technique in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction tumors larger than 5 cm].

Objective: To investigate the safety and feasibility of laparoscopic double-flap technique (Kamikawa) in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction (EGJ) leiomyoma and gastrointestinal stromal tumor (GIST) with the maximum diameter >5 cm. Methods: A descriptive case-series study was used to retrospectively analyze the data of patients with EGJ leiomyoma and GIST undergoing laparoscopic-assisted proximal gastrectomy and double-flap technique (Kamikawa) at the Department of Gastrointestinal Surgery, Guangdong Hospital of Traditional Chinese Medicine from September 2017 to March 2019. All the tumors invaded the cardia dentate line, and the maximum diameter was >5 cm. After the exclusion of patients requiring emergency surgery and complicating with severe cardiopulmonary diseases, a total of 4 patients, including 3 males and 1 female with age of 29-49 years, were included in this study. After laparoscopic-assisted proximal gastrectomy, the residual stomach was pulled out of the abdominal cavity and marked with methylene blue at the proximal end 3~4 cm from the anterior wall of the residual stomach in the shape of "H". The gastric wall plasma muscular layer was cut along the "H" shape, and the space between the submucosa and the muscular layer was separated to both sides along the longitudinal incision line to make the seromuscular flap. The residual stomach was put back into the abdominal cavity. Under laparoscopy, 4 stitches were intermittently sutured at the upside of "H" shape and 4-5 cm from the posterior wall of the esophageal stump. The stump of the esophagus was cut open, and the submucosa and mucosa were cut under the "H" shape to enter the gastric cavity. The posterior wall of the esophageal stump was sutured continuously with the gastric stump mucosa and submucosa under laparoscopy. The anterior wall of the esophageal stump was sutured continuously with the whole layer of the residual stomach. The anterior wall of the stomach was sutured to cover the esophagus. The anterior gastric muscle flap was sutured and embedded in the esophagus to complete the reconstruction of digestive tract. The morbidity of intraoperative complications and postoperative reflux esophagitis and anastomosis-related complications were observed. Results: All the 4 patients completed the operation successfully, and there was no conversion to laparotomy. The median operative time was 239 (192-261) minutes, the median Kamikawa anastomosis time was 149 (102-163) minutes, and the median intraoperative blood loss was 35 (20-200) ml. The abdominal drainage tube and gastric tube were removed, and the fluid diet was resumed on the first day after surgery in all the 4 patients. The median postoperative hospitalization time was 6 (6-8) days. Postoperative pathology revealed 3 leiomyomas and 1 GIST. There were no postoperative complications such as anastomotic leakage or stenosis, and no reflux symptoms were observed. The median follow-up time was 22 (11-29) months after the operation, and no reflux esophagitis occurred in any of the 4 patients by gastroscopy. Conclusion: For >5 cm EGJ leiomyoma or GIST, double-flap technique (Kamikawa) used for digestive tract reconstruction after proximal gastrectomy is safe and feasible.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

Effects of dietary pyrroloquinoline quinone disodium supplementation on inflammatory responses, oxidative stress, and intestinal morphology in broiler chickens challenged with lipopolysaccharide.

This study was conducted to investigate the effects of pyrroloquinoline quinone disodium (PQQ·Na2) on inflammatory responses, oxidative stress, and intestinal morphology of broiler chickens challenged with lipopolysaccharide (LPS). A 2 × 2 factorial arrangement in a complete randomized design experiment was used to study the effect of dietary PQQ·Na2 (0 or 1 mg/kg) on broiler chickens with or without a challenge with LPS. A total of two hundred eighty-eight 1-day-old Arbor Acre broiler chickens were randomly assigned to 4 treatments with 6 replicate cages of 12 birds per cage. All experimental broilers were injected intraperitoneally with 0.5 mg/kg body weight of either Escherichia coli LPS or sterile saline at 16, 18, and 20 d of age. Results showed that injecting LPS significantly increased the concentrations of interleukin-1beta (IL-1ß) in serum of birds on day 20 and day 21. Meanwhile, LPS injection increased (P < 0.05) the relative mRNA expression of interleukin-6 (IL-6) in the duodenal mucosa of broilers on day 21. However, dietary supplementation with PQQ·Na2 decreased (P < 0.05) the concentration of IL-6 in serum of birds on day 20 and the levels of IL-1ß, IL-6, and interleukin-10 (IL-10) in serum of broiler chickens on day 21. Besides, supplementation of PQQ·Na2 within diet decreased (P < 0.05) the mRNA expressions of IL-1ß and IL-10 in the duodenal mucosa of birds on day 20. Relative to saline injection, the activity of glutathione peroxidase (GSH-Px) in serum and the activities of total superoxide dismutase (T-SOD) and catalase (CAT) in liver were found to be lower (P < 0.05) in broilers after LPS challenge on day 21. However, birds fed with PQQ·Na2 showed higher (P < 0.05) GSH-Px activity in serum and higher (P < 0.05) T-SOD activities in liver on day 21 and day 42. Pyrroloquinoline quinone disodium also significantly attenuated the LPS-induced decreases in villus height to crypt depth ratio in the duodenum of broilers. In conclusion, dietary PQQ·Na2 supplementation significantly exerted protective effects on inflammation damage and oxidant stress of broilers under LPS challenge by regulating the expression of inflammatory cytokines (IL-1ß, IL-6, and IL-10) and activities of antioxidant enzymes (GSH-Px, T-SOD, and CAT). Moreover, dietary PQQ·Na2 supplementation significantly ameliorated the LPS-impaired intestinal morphology in broilers. Therefore, it has been considered that PQQ·Na2 can be used as a potential feed additive in broiler production.

Antibacterial Effects of Schisandra chinensis Extract on Escherichia coli and its Applications in Cosmetic.

Schisandra chinensis (Turcz.) Baill (S. chinensis), an edible traditional medicine herb, has a strong constitution, which extract has good antibacterial activity. The study investigated its antibacterial properties on E. coli, to find a candidate for the development as new preservative. In vitro antibacterial assay showed that S. chinensis extract (SCE) effectively inhibited the growth of test bacteria with MBC of 18 mg/mL. In model cosmetic system of O/W emulsions, SCE possessed a great antibacterial capacity. The growth curves of E. coli treated with SCE exhibited an extended lag phase and restricted log phase. Scanning electron microscopy showed that the treated E. coli cells exhibited wrinkled and withered surfaces, and disappearing outmost layer, suggesting S. chinensis extract can damage S. aureus cell member and wall, in addition, the leakage of periplasm enzyme AKPase and the increased activities of Na+/K+-ATPase and Ca++-ATPase in cell membrane were also consistent with the microscopy results. Moreover, the S. chinensis extract can decrease the activities of dehydrogenase and total ATPase and the content of intracellular proteins, and bind with S. aureus DNA by electrostatic and groove binding. The results indicated that SCE might be a candidate cosmetic preservative for its good antibacterial activity and multiple targets on E. coli.

Effects of dietary Zn-methionine supplementation on the laying performance, egg quality, antioxidant capacity, and serum parameters of laying hens.

This study was to determine the effects of dietary Zn-methionine (Zn-Met) supplementation on the laying performance, egg quality, antioxidant capacity, and serum parameters of laying hens. Jingh ong-1 strain laying hens (n = 720, 49 wk of age) were randomly assigned to 6 treatments with 6 replications of 20 birds. The control was fed a basal diet supplemented with 80 mg of Zn/kg as Zn sulphate of diet and the 5 groups were fed a basal diet supplemented with 20, 40, 60, 80, and 100 mg of Zn/kg as Zn-Met of diet for 10 wk, respectively. At the terminal experiment, there were significant differences between control and 80 mg/kg Zn-Met group in feed intake (P < 0.05) and feed conversion ratio (FCR) (P < 0.01). Egg weight (P < 0.05) and albumen height (P < 0.01) reduced and were not significantly influenced by supplemental 80 mg/kg Zn-Met group until being stored 15 d as compared to the control. Zn-Met group in 100 mg/kg significantly increased haugh unit (P < 0.05) as compared to the control. The activity of MDA in serum had a linear decrease in 20 to 100 mg/kg Zn-Met. The activity of CAT in liver and GSH-Px in serum had quadratic effects in response to the Zn-Met treatments. Compared to the control, 60 mg/kg Zn-Met group increased the T-AOC, GSH-Px activity in serum (P < 0.01), and the T-AOC (P < 0.05), CuZnSOD (P < 0.01), GSH-Px (P < 0.01) activity in liver. Compared with the control, the concentration of serum ionic Ca in 80, 100 mg/kg Zn-Met treatments reduced (P < 0.01) significantly while the activity of serum alkaline phosphatase (AKP) increased in the Zn-Met groups of 40, 60, and 80 mg/kg (P < 0.01), and 100 mg/kg (P < 0.05). In conclusion, dietary Zn-Met supplementation at 60 to 80 mg/kg had more positive effects on performance, egg quality, and antioxidant capacity in laying hens as compared to 80 mg/kg ZnSO4.

Effects of dietary supplementation with Clostridium butyricum on laying performance, egg quality, serum parameters, and cecal microflora of laying hens in the late phase of production.

This experiment was conducted to evaluate the effects of dietary supplementation with Clostridium butyricum on laying performance, egg quality, serum parameters, and cecal microflora of laying hens in the late phase of production. Jinghong-1 strain laying hens (n = 960; 48 wk of age) were randomly allocated to 5 treatment groups with 6 replicates of 32 hens. Hens were fed with basal diet (control) and basal diet supplemented with 2.5 × 104 (CB1), 5 × 104 (CB2), 1 × 105 (CB3), and 2 × 105 (CB4) cfu/g C. butyricum for 10 wk. The results showed that egg production, egg mass, and eggshell strength increased quadratically as supplemental C. butyricum increased, and these responses were maximized in the CB2 group (P < 0.05). Compared with the control group, the addition of C. butyricum resulted in quadratic effects on serum total protein, uric acid, calcium, complement component C3 and catalase concentrations, and these responses were maximized or minimized in the CB2 group (P < 0.05). Linear and quadratic increases were observed in serum IgM, total superoxide dismutase, and glutathione peroxidase concentrations, and these responses were maximized in CB2 or CB3 group (P < 0.05). The addition of C. butyricum in the CB2 group resulted in linearly increasing levels of serum IgG concentration as compared with the control group (P < 0.05). Spleen index increased (P < 0.05) in the CB2 group. Hens fed with C. butyricum reduced (P > 0.05) the population of E. coli, while Bifidobacterium counts increased quadratically and maximized in the CB2 group (P < 0.05). In conclusion, the results indicated that dietary supplementation with C. butyricum (5 × 104 or 1 × 105 cfu/g) could improve laying performance and egg quality by promoting immune function, enhancing antioxidative capacity, and benefiting the cecal microflora of laying hens in the late phase of production.

Removal of prometryn from hydroponic media using marsh pennywort (Hydrocotyle vulgaris L.).

The aquatic plant Hydrocotyle vulgaris was evaluated for its efficacy in removing prometryn from nutrient solution. Under optimized experimental conditions, up to 94.0% of the initial prometryn was removed from the hydroponic culture medium by H. vulgaris in 30 days. The concentration of prometryn decreased from the initial level of 0.55 ± 0.013 mg/L to 0.036 ± 0.001 mg/L at the end of the experimental period. The removal kinetics followed first-order kinetic equation (Ct = 0.4569e-0.09t). Half-life (t1/2) of prometryn was greatly shortened from 27.16 days (without plant) to 5.58 days (with H. vulgaris). Approximately 22% of the initial prometryn residue was found in H. vulgaris tissue, while 11.7% was degraded by the plant in 30 days. The metabolites of prometryn detected were 2,4-diamino-1,3,5-triazine (in the hydroponic culture medium) and 2,4,6-trihydroxy-1,3,5-triazine (in plant tissue) after 30 days. The results indicate that H. vulgaris can be used for phytoextraction of prometryn and could potentially be effective in removing other s-trazine pesticides from contaminated aquatic ecosystems.

Effects of AttM lactonase on the pathogenicity of Streptomyces scabies.

The biosynthesis of phytotoxin thaxtomin A (TXT) constitutes the major pathogenicity determinant in Streptomyces scabies, the most widely studied phytopathogen causing scab disease in potato and other root crops. It is recognized that S. scabies regulates its pathogenicity via γ-butyrolactone (GBL)-dependent quorum sensing (QS) signalling. AttM, from Agrobacterium tumefaciens C58 strain, has recently been proposed to have GBL-assimilative capacity. Here, we presented the introduction of A. tumefaciens-derived attM gene into S. scabies using the Escherichia coli-Streptomyces shuttle vector pIJ8600 via intergeneric conjugation, followed by the investigation of secondary metabolism (mycelium growth, TXT production and pathogenicity) in S. scabies attM exconjugants (S.s/attM) in comparison with their wild-type parent strain (S.s/WT). Among the resultant S.s/attM exconjugants, attM was found to be integrated into S. scabies chromosome as analysed by Southern blotting. Moreover, S.s/attM failed to evoke the disease symptoms in planta and displayed altered morphological differentiation in contrast to S.s/WT. The abolishment of TXT production in S.s/attM substantiated the loss of pathogenicity and also implied that attM, when constitutively expressed in S. scabies, could paralyse its GBL signalling pathway. Altogether, lactonase-coding gene attM would be useful in a quorum quenching strategy for plant protection via suppressing TXT production and pathogenicity of S. scabies. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an efficient means to introduce the lactonase gene attM from Agrobacterium tumefaciens into Streptomyces scabies for evaluating the role of γ-butyrolactone (GBL) in thaxtomin A production and pathogenicity, etc. Our results showed that pathogenicity was abrogated in attM-expressing S. scabies exconjugants. Although there are gene knockout approaches to inactivating GBL signalling and thus pathogenicity in S. scabies, they are not only time consuming due to refractory host but also possibly incomplete in view of gene redundancy. Our work is the first report for a kind of lactonase affecting pathogenicity and/or virulence of scab-causing Streptomyces species.

Dietary butylated hydroxytoluene improves lipid metabolism, antioxidant and anti-apoptotic response of largemouth bass (Micropterus salmoides).

A 10-week growth trail was conducted to investigate the efficacy and tolerance of dietary butylated hydroxytoluene (BHT) by evaluating inflammation, apoptosis and hepatic disease related to oxidative stress in largemouth bass (Micropterus salmoides). Four experimental diets were prepared with BHT supplement levels of 0 (B0), 150 (B150), 300 (B300) and 1500 (B1500) mg/kg, in which B150 was at the maximum recommended level established by European Union Regulation, and the B300 and B1500 levels were 2 and 10-fold of B150, respectively. Each diet was fed to 6 replicates with 30 largemouth bass (initial body weight, IBW = 6.20 ± 0.01 g) in each tank. The BHT inclusion level did not affect the specific growth rate, but fish in the B150 group showed the lowest feed conversion rate (P < 0.05). BHT inclusion significantly decreased the levels of plasma TC, TG, LDL, ALT and AKP, and increased the (HDL-C)/TC ratio (P < 0.05). Plasma MDA was significantly decreased in the B150 group and GSH-Px was extremely enhanced in each BHT inclusion group (P < 0.05). Hepatic T-AOC was significantly enhanced and O2- was significantly decreased in each BHT inclusion group compared to the B0 group (P < 0.05), as well as hepatic MDA was significantly decreased in B1500 group (P < 0.05). Dietary BHT inclusion down-regulated the hepatic mRNA levels of inflammation, apoptosis and fibrosis related genes, including TNFα, TGF-ß1, α-SMA, IL8, IL11ß and caspase-9. Moreover, BHT could improve hepatic lipid metabolism via up-regulating the mRNA levels of APOA1, CYP7A1, CYP8B1, and down-regulating the mRNA levels of PPAR-γ and APOB. Histological examination of the liver morphology with H&E and Sirius Red staining showed that BHT inclusion decreased necrotic degenerative changes and collagen deposition in largemouth bass. An immunofluorescence examination revealed significantly decreased cleaved caspase-3 signals in the BHT groups. In conclusion, the results demonstrated that ROS induces hepatic cell apoptosis and fibrosis via the intrinsic pathway of apoptosis by activating caspase-9 in the mitochondria and then initiates apoptosis by activating caspase-3. Consuming 2.32-23.80 mg/kg·bw/d (150-1500 mg/kg in diet) of BHT effectively improved the plasma and hepatic lipid metabolism, antioxidant response as well as reduced ROS production, protecting hepatic cells from injury. It is implied that even a 10-fold increase of the maximum level of BHT (150 mg/kg) is safe for the largemouth bass.

Novel polysaccharide binding to the N-terminal tail of galectin-3 is likely modulated by proline isomerization.

Interactions between galectins and polysaccharides are crucial to many biological processes, and yet these are some of the least understood, usually being limited to studies with small saccharides and short oligosaccharides. The present study is focused on human galectin-3 (Gal-3) interactions with a 60 kDa rhamnogalacturonan RG-I-4 that we use as a model to garner information as to how galectins interact with large polysaccharides, as well as to develop this agent as a therapeutic against human disease. Gal-3 is unique among galectins, because as the only chimera-type, it has a long N-terminal tail (NT) that has long puzzled investigators due to its dynamic, disordered nature and presence of numerous prolines. Here, we use 15N-1H heteronuclear single quantum coherence NMR spectroscopy to demonstrate that multiple sites on RG-I-4 provide epitopes for binding to three sites on 15N-labeled Gal-3, two within its carbohydrate recognition domain (CRD) and one at a novel site within the NT encompassing the first 40 residues that are highly conserved among all species of Gal-3. Moreover, strong binding of RG-I-4 to the Gal-3 NT occurs on a very slow time scale, suggesting that it may be mediated by cis-trans proline isomerization, a well-recognized modulator of many biological activities. The NT binding epitope within RG-I-4 appears to reside primarily in the side chains of the polysaccharide, some of which are galactans. Our results provide new insight into the role of the NT in Gal-3 function.

Danggui Buxue Tang, a simple Chinese formula containing Astragali Radix and Angelicae Sinensis Radix, stimulates the expressions of neurotrophic factors in cultured SH-SY5Y cells.

BACKGROUND: Danggui Buxue Tang (DBT), a phytoestrogen-enriched Chinese herbal formula, serves as dietary supplement in stimulating the "Blood" functions of menopausal women. In traditional Chinese medicine (TCM) theory, "Blood" has a strong relationship with brain activities. Previous studies supported that some ingredients of DBT possessed neuronal beneficial functions. Therefore, the neurotrophic function and the mechanistic action of DBT were systematically evaluated in cultured human neuroblastoma SH-SY5Y cells. METHODS: The DBT-triggered protein expressions were analyzed by western blotting, while the transcriptional activities of promoters coding for related genes were revealed by luciferase assays. For mechanistic analysis of DBT, Erk1/2 and its inhibitor U0126 were analyzed. RESULTS: The application of DBT in cultured neuroblastoma cells showed the efficacies in: (1) up-regulation of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF); (2) activation of transcriptional activities of promoters coding for NGF, BDNF, GDNF; (3) activation of Erk1/2 and CREB; and (4) attenuation of the neurotrophic factor expression by the treatment of an Erk1/2 inhibitor. CONCLUSIONS: Our study supports that MAPK/Erk pathway acts as fundamental role in monitoring DBT-induced expression of neurotrophic factors in cultured human neuroblastoma cell. These results shed light in developing the working mechanism of this ancient herbal decoction for its neuronal function.

Protective effects of fraction 4a of polysaccharides isolated from Lycium barbarum against KBrO3-induced renal damage in rats.

Potassium bromate (KBrO3) is widely used as a food additive and is a major by-product of water disinfection. The aim of this study was to investigate the protective effects of fraction 4a of polysaccharides isolated from Lycium barbarum (LBP-4a) against renal damage induced by KBrO3 in rats and to determine the relevant mechanisms behind these effects. Male Wistar rats were divided into a normal control group, a KBrO3 control group, and LBP-4a(L) and LBP-4a(H) groups. With the exception of the normal control group, the rats in the other three groups were administered KBrO3 by intraperitoneal injection to induce renal damage. Before the induction of renal damage, rats in the LBP-4a(L) and LBP-4a(H) groups were pretreated with 50 mg per kg b.w. or 100 mg per kg b.w. LBP-4a, respectively, by intragastric administration. Clinical biochemical parameters and markers of oxidative damage were also determined. Treatment by administration of LBP-4a prior to challenge with KBrO3 prevented increases in the levels of nitrite, creatinine, urea nitrogen and uric acid in serum and increased the activities of antioxidant enzymes in kidney tissues. A comet assay and FCS results showed that pretreatment with LBP-4a also alleviated DNA damage and decreases in mitochondrial membrane potentials in renal cells. Histological studies further supported the above results and showed extensive renal damage in animals treated with KBrO3 and greatly reduced tissue injury in groups pretreated with LBP-4a. In conclusion, LBP-4a exhibited protective effects against renal damage induced by KBrO3, and the mechanism was closely correlated with a reduction in levels of lipid peroxidation and an increase in the activities of antioxidant enzymes in kidney tissues, which alleviated DNA damage and increased mitochondrial membrane potentials in renal cells. These observations provide the background for the further development of LBP-4a as a protective agent for use in the treatment of renal damage.

[The prospects of the biotherapy for refractory uveitis].

Noninfectious uveitis is a kind of recurrent autoimmune disease and a major cause of blindness in clinical practice. Corticosteroids are the conventional medication, but have severe side effects for long-term users, and some refractory patients are treated with immunosuppressive agents. Because the pathogenesis of uveitis is related to the autoimmune imbalance mediated by CD4 + T lymphocytes. The macrophages, lymphocytes and some cytokines are involved. The immunomodulatory therapy is targeted to block the lymphocytes, cytokines or their receptors, so as to control the inflammatory damage or minimize the recurrence of the disease. The biological agents include the anti-tumor necrosis factor agents, interferon-α, interleukin receptor antagonists, cytotoxic T lymphocyte associated antigen fusion proteins and CD20 chimeric antibody. They bring a hope for the treatment of the patients with refractory uveitis. Because of the limited number of randomized clinical trials and patients, the indications, long-term effects, safety and side effects of these biologics need to be observed. In this article, the experiments and clinical trials of these new biologics for the treatment of uveitis in recent years are reviewed. (Chin J Ophthalmol, 2016, 52: 551-556).