Effects of dietary addition of ellagic acid on rumen metabolism, nutrient apparent digestibility, and growth performance in Kazakh sheep.

Plant extracts have shown promise as natural feed additives to improve animal health and growth. Ellagic acid (EA), widely present in various plant tissues, offers diverse biological benefits. However, limited research has explored its effects on ruminants. This study aimed to investigate the effects of dietary addition EA on rumen metabolism, apparent digestibility of nutrients, and growth performance in Kazakh sheep. Ten 5-month-old Kazakh sheep with similar body weight (BW), fitted with rumen fistulas, were randomly assigned to two groups: the CON group (basal diet) and the EA group (basal diet + 30 mg/kg BW EA). The experiment lasted 30 days, and individual growth performance was assessed under identical feeding and management conditions. During the experimental period, rumen fluid, fecal, and blood samples were collected for analysis. The results indicated a trend toward increased average daily gain in the EA group compared to the CON group (p = 0.094). Compared with the CON group, the rumen contents of acetic acid and propionic acid were significantly increased in the EA group and reached the highest value at 2 h to 4 h after feeding (p < 0.05). Moreover, the relative abundances of specific rumen microbiota (Ruminococcaceae, uncultured_rumen_bacterium, unclassified_Prevotella, Bacteroidales, Bacteroidota, Bacteroidia, unclassified_Rikenellaceae, and Prevotella_spBP1_145) at the family and genus levels were significantly higher in the EA group (p < 0.05) compared to the CON group. The EA group exhibited significantly higher dry matter intake (p < 0.05) and increased the digestibility of neutral detergent fiber and ether extract when compared with the CON group (p < 0.05). Additionally, the plasma activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly higher, while malondialdehyde (MDA) concentration was significantly lower in the EA group compared to the CON group (p < 0.05). In conclusion, dietary supplementation with 30 mg/kg BW EA in 5-month-old Kazakh sheep increased the dry matter intakQ16e, apparent digestibility of neutral detergent fiber, and ether extract, as well as the contents of acetic acid and propionic acid in rumen fluid. Moreover, EA supplementation regulated the ruminal microbiota, enhanced antioxidant capacity, and improved daily weight gain.

Effects of Lactobacillus rhamnosus Supplementation on Growth Performance, Immune Function, and Antioxidant Capacity of Newborn Foals.

This study aimed to explore the effects of Lactobacillus rhamnosus GG (LGG) supplementation on the growth performance, immune function, and antioxidant capacity of foals. Fifteen newborn foals with similar birth weight (51.67 ± 6.07 kg) and good health were randomly assigned to three groups: control group and test groups I and II, which were supplemented with 5.0 × 109 CFU/day and 1.0 × 1010 CFU/day LGG, respectively, for 150 days. LGG intake increased the daily body height (P < .01) and weight (P < .01) gain of foals aged 120 to 150 days. The foals' IgA (P < .05) and IgG (P < .01) plasma levels increased at 30 and 150 days, respectively, and IL-6 plasma level increased at 90 days (P < .01). Plasma total antioxidant capacity level was significantly higher in test group I than in the control and test group II at 30 days (P < .01), whereas glutathione peroxidase level was significantly higher in test group II than in the control and test group I at 30 days (P < .01). Both test groups had significantly higher superoxide dismutase level than the control group (P < .01) and significantly decreased malondialdehyde plasma level at 90 and 150 days (P < .05). Overall, our findings indicate that dietary supplementation of LGG can improve the growth performance, immune function, and antioxidant capacity of newborn foals.

Secondary Squamous Cell Carcinoma of Prostate: A Case Report.

BACKGROUND: Among prostate cancer, primary prostate squamous cell carcinoma (SCC) is a rare condition with low incidence, and secondary prostate SCC is rarer with fewer cases reported globally. This report presents an extremely rare case of secondary prostate SCC that metastasised from lung cancer. CASE PRESENTATION: This study reports the case of a 77-year-old man who presented with acute urinary retention and dysuria and was admitted to our hospital. Physical and digital rectal examinations were conducted and revealed the overfilling of the suprapubic bladder and a slightly enlarged prostate without palpable nodules, respectively. The patient was tested negative for total and free prostate antigens (PSA) and had large masses in the upper lobes of both lungs and an irregularly enlarged prostate in the computed tomography images. The patient was inserted immediately with 18F triple-cavity Foley catheter to drain haematuria with blood clots. The patient was treated with electric coagulation haemostasis and transurethral resection of the prostate and subjected to postoperative histopathological analysis, which revealed the diagnosis of SCC. The patient was advised to undergo further radiation therapy and chemotherapy but rejected all follow-up treatments for lungs and prostate. The patient recovered uneventfully and was discharged 7 days after the operation. The patient remained alive after 6 months of follow-up. CONCLUSIONS: Secondary prostate SCC is an extremely rare type of tumour. Surgical intervention plays a role in stopping bleeding and relieving urination problems, and timely treatment may led to favourable prognosis.

Effect of ellagic acid on body weight, nutrient digestibility, fecal microbiota, and urolithin A metabolism in Thoroughbred horses.

This study aimed to investigate the effects of ellagic acid (EA) supplementation on body weight (BW), nutrient digestibility, fecal microbiota, blood biochemical indices, and urolithin A metabolism in 1-yr-old Thoroughbred horses. A group of 18 1-yr-old Thoroughbred horses, with an average weight of 339.00 ±â€…30.11 kg, were randomly allocated into three groups of six horses each (three males and three females). The control group (n = 6) received only the basal diet, whereas test groups I (n = 6) and II (n = 6) were fed the basal diet supplemented with 15 mg/kg BW/d and 30 mg/kg BW/d of EA, respectively, for 40-d. The results showed that test group I and II horses had a significant increase in total weight gain by 49.47% and 62.74%, respectively, compared to the control group. The digestibility of various components in the diets of the test group horses was improved, including dry matter, organic matter, gross energy, neutral detergent fiber, acid detergent fiber, and calcium. Additionally, the digestibility of crude protein and phosphorus (P) in test group II horses increased significantly by 10.96% and 33.56% (P < 0.05), respectively. Moreover, EA supplementation significantly increased the fecal abundance of Firmicutes, Bacteroidetes (P < 0.05), Fibrobacterota, p-251-o5, Desemzia incerta (P < 0.05), and Fibrobacter sp. (P < 0.05), while reducing the abundance of Proteobacteria, Pseudomonadaceae, Pseudomonas, and Cupriavidus pauculus (P < 0.05 or P < 0.01). Fecal samples from test group II showed 89.47%, 100%, and 86.15% increases in the concentrations of acetic acid, valeric acid, and total volatile fatty acids, respectively. In addition, the plasma levels of total protein, and globulin increased significantly in test groups I (7.88% and 11.35%, respectively) and II (13.44% and 16.07%, respectively) compared to those in the control group (P < 0.05). The concentration of urolithin A in fecal and urine samples was positively correlated with increasing doses of EA. These findings suggest that supplemental feeding of EA improved nutrient digestibility, blood biochemical indices, and fecal microbiota in 1-yr-old Thoroughbred horses, promoting growth and development.

Ellagic acid (EA), a plant-derived feed additive, has beneficial physiological effects, including antioxidant and anti-inflammatory properties as well as intestinal microbiota regulation. Young Thoroughbred horses exhibit rapid growth and require ample nourishment. However, the underdeveloped functional anatomy of their gastrointestinal tract restricts the rate of feed utilization. Therefore, improving digestive tract function in horses at this stage promotes intestinal homeostasis, improves antioxidant and anti-inflammatory capabilities, and supports rapid growth and health. This study revealed that supplemental feeding of 1-yr-old Thoroughbred horses with EA improved nutrient digestibility and fecal floral diversity, leading to enhanced growth performance. The optimal dose was 30 mg/kg body weight.

LC-MS Analysis of Ginsenosides in Different Parts of Panax quinquefolius and Their Potential for Coronary Disease Improvement.

Seven main ginsenosides, including ginsenoside Re, ginsenoside Rb1, pseudoginsenoside F11, ginsenoside Rb2, ginsenoside Rb3, ginsenoside Rd, and ginsenoside F2, were identified by LC-QTOF MS/MS from root, leaf and flower extracts of Panax quinquefolius. These extracts promoted intersegmental vessel growth in a zebrafish model, indicating their potential cardiovascular health benefits. Network pharmacology analysis was then conducted to reveal the potential mechanisms of ginsenoside activity in the treatment of coronary artery disease. GO and KEGG enrichment analyses elucidated that G protein-coupled receptors played a critical role in VEGF-mediated signal transduction and that the molecular pathways associated with ginsenoside activity are involved in neuroactive ligand-receptor interaction, cholesterol metabolism, the cGMP-PKG signaling pathway, etc. Moreover, VEGF, FGF2, and STAT3 were confirmed as the major targets inducing proliferation of endothelial cells and driving the pro-angiogenic process. Overall, ginsenosides could be potent nutraceutical agents that act to reduce the risks of cardiovascular disease. Our findings will provide a basis to utilize the whole P. quinquefolius plant in drugs and functional foods.

Graphene-based nanomaterials for cancer therapy and anti-infections.

Graphene-based nanomaterials (GBNMs) has been thoroughly investigated and extensively used in many biomedical fields, especially cancer therapy and bacteria-induced infectious diseases treatment, which have attracted more and more attentions due to the improved therapeutic efficacy and reduced reverse effect. GBNMs, as classic two-dimensional (2D) nanomaterials, have unique structure and excellent physicochemical properties, exhibiting tremendous potential in cancer therapy and bacteria-induced infectious diseases treatment. In this review, we first introduced the recent advances in development of GBNMs and GBNMs-based treatment strategies for cancer, including photothermal therapy (PTT), photodynamic therapy (PDT) and multiple combination therapies. Then, we surveyed the research progress of applications of GBNMs in anti-infection such as antimicrobial resistance, wound healing and removal of biofilm. The mechanism of GBNMs was also expounded. Finally, we concluded and discussed the advantages, challenges/limitations and perspective about the development of GBNMs and GBNMs-based therapies. Collectively, we think that GBNMs could be potential in clinic to promote the improvement of cancer therapy and infections treatment.

Cleaning Disposal of High-Iron Bauxite Residue Using Hydrothermal Hydrogen Reduction.

The hydrothermal hydrogen reduction process for treating high-iron bauxite residue (red mud) was investigated, and the optimum conditions of alumina extraction as well as the enrichment of iron minerals were verified by experiments. Results show that the surface magnetization of Al-goethite under the function of hydrogen reduction accelerates its conversion to hematite and/or magnetite. This conversion releases the substituted Al in goethite as well as the undigested gibbsite/boehmite and further enriches the iron content in residue. After hydrothermal hydrogen reduction with H2/Red mud ratio of 0.085 mol/20 g at 270°C for 60 min, the alumina relative recovery ratio reaches 95.40% and the grade of iron (total iron in the form of iron element) in the residue can be enriched to 55.85%. Further, co-processing of the obtained iron-rich residue in the steel industry can achieve a significant reduction of red mud discharge.

Effects of dietary guanidinoacetic acid on growth performance, guanidinoacetic acid absorption and creatine metabolism of lambs.

Guanidinoacetic acid (GAA) is the only precursor for the creatine synthesis of vertebrates. Creatine (Cr) and phosphocreatine (PCr) are able to provide energy for the rapid growth and development of the muscle tissue. This study evaluated the effects of dietary different levels GAA on growth performance, GAA absorption and creatine metabolism of lambs. Twenty-four 3-month-old healthy Kazakh male lambs (body weight = 27.35± 0.58 kg) were randomly divided into four groups with 6 lambs in each group. The lambs were fed with the basal diets supplemented with 0 (0 mg/kg group), 500 (500 mg/kg group), 1000 (1000 mg/kg group) and 1500 mg (1500 mg/kg group) GAA per kg diet (DM basis), respectively. The results showed that, as the GAA content of the diet increased, there was a quadratic change in DMI, with the lowest in the 500 mg/kg group and the highest in the 0 mg/kg group. The CK enzyme activity and ATP content in quadriceps muscle increased linearly with increasing levels of diary GAA in the diet. PCr levels and ADP levels in the longest dorsal muscle increased linearly with increasing levels of GAA in the diet. The relative expression of SLC6A6 and SLC6A8 mRNA in the jejunum and ileum mucosa showed a quadratic change as the dietary GAA level increased, with the lowest relative expression in both the 1500 mg/kg group. With the increase of dietary GAA level, both Cr concentration in hepatic vein plasma and the portal plasma GAA concentration shows a quadratic change, with the highest concentration in the 500 mg/kg group and the lowest concentration in the 0 mg/kg group. Therefore, dietary supplementation with 500~1000 mg/kg DM GAA is recommended for lambs.

Preparation and characterization of young Prunus persica fruit fraction and its anti-inflammatory effect on a transgenic zebrafish model.

Young Prunus persica fruits (YPF) contain substances that are distinct from those found in the mature fruits. Response surface methodology was used to explore the influences of extraction conditions including ultrasonic time (X1), ethanol proportion (X2), liquid-to-solid ratio (X3) and temperature (X4) on UV-absorbing components from YPF. To purify the extract, the adsorption/desorption properties of 280 nm-absorbing components on AB-8 resin were investigated. A total of 11 metabolites (amino acids, glycosylated amino acids and phenolics) were identified in the UV-absorbing fraction of YPF (YPF-F) based on LC-MS/MS assays. In a study of in vivo anti-inflammatory activity, YPF-F significantly decreased the number of inflammatory cells that migrated to the lateral line location in CuSO4-induced transgenic fluorescent zebrafish. YPF should be utilized as a high value resource of functional foods.[Formula: see text].

Hostaflavone A from Hosta plantaginea (Lam.) Asch. blocked NF-κB/iNOS/COX-2/MAPKs/Akt signaling pathways in LPS-induced RAW 264.7 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Hostaflavone A (HA) is a new flavonoid component isolated from the flower of Hosta plantaginea (Lam.) Asch., which is commonly used as a folk herbal to treat inflammatory diseases in China. Nevertheless, the anti-inflammatory effect of HA remains unknown. AIM OF THE STUDY: This work aimed to evaluate the HA with anti-inflammatory activity and mechanism in RAW 264.7 macrophages activated by lipopolysaccharide (LPS). MATERIALS AND METHODS: Anti-inflammatory effect of HA was evaluated by measuring of cell viability, nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6 levels in RAW 264.7 cells. In parallel, the HA action mechanism of nuclear factor kappa B (NF-κB) p65, inhibitor of NF-κB (IκB), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (Erk), p38, and protein kinase B (Akt) were detected by Western blot analysis. RESULTS: HA has no cytotoxicity at concentrations as high as 40 µM. Besides, HA concentration-dependently clearly suppressed the overproduction of NO, PGE2, TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS. In addition, HA remarkably reduced the upregulation of phosphorylated NF-κB p65, phosphorylated IκB, phosphorylated JNK, phosphorylated Erk and phosphorylated p38, together with iNOS and COX-2 protein expressions in a concentration-dependent manner. CONCLUSION: HA blocked the LPS activated inflammation via suppressing NF-κB, iNOS, COX-2, mitogen-activated protein kinases (MAPKs) and Akt pathways in RAW 264.7 cells, and might be a new anti-inflammatory agent.

Region-Specific Biomarkers and Their Mechanisms in the Treatment of Lung Adenocarcinoma: A Study of Panax quinquefolius from Wendeng, China.

Panax quinquefolius, a popular medicinal herb, has been cultivated in China for many years. In this work, the region-specific profiles of metabolites in P. quinquefolius from Wendeng was investigated using liquid-chromatography-quadrupole-time-of-flight-(LC-Q-TOF)-based metabolomics analysis. The three most abundant biomarkers, identified as ginsenoside Rb3, notoginsenoside R1, and ginsenoside Rc, were the representative chemical components employed in the network pharmacology analysis. In addition, molecular docking and western blotting analyses revealed that the three compounds were effective binding ligands with Hsp90α, resulting in the inactivation of SRC and PI3K kinase, which eventually led to the inactivation of the Akt and ERK pathways and lung cancer suppression. The outcomes obtained herein demonstrated the intriguing chemical characteristics and potential functional activities of P. quinquefolius from Wendeng.

Anti-inflammatory peptides and metabolomics-driven biomarkers discovery from sea cucumber protein hydrolysates.

The hydrolysates from Apostichopus japonicus sea cucumber are an important source of nitrogen that may be added to foods. We evaluated the effect of A. japonicus hydrolysates on inflammation-associated leukocyte recruitment. The results revealed that leukocyte migration to the site of injury was significantly blocked by AJH-1 (<10 kDa), suggesting a protective effect against CuSO4 -induced neuromast damage in a zebrafish model. Based on liquid chromatography/time-of-flight/mass spectrometry, and metabolomic analysis, the nine biomarker candidates in AJH-1 were Val, Ala-Pro-Arg, Gly-Lys, Asp propyl ester, Glu methyl ester, His butyl ester, Ile-Ala-Ala-Lys, Tyr-Lys, and Asn-Pro-Gly-Lys. We used molecular docking to predict the binding affinity and docked position of the peptides onto the angiotensin converting enzyme (ACE). All the identified peptides had adequate binding affinity toward ACE, especially peptides Ala-Pro-Arg and Gly-Lys. These peptides may be used in the development of therapeutic foods. PRACTICAL APPLICATION: The study revealed the anti-inflammatory properties of the fractionated sea cucumber protein hydrolysate (<10 kDa). The characteristic peptides may be used as functional ingredients in nutraceutical foods and beverages.

Bioequivalence of a Generic Nateglinide Formulation in Healthy Chinese Volunteers under Fasting and Fed Conditions: A Randomized, Open-Label, Double-Cycle, Double-Crossover Study.

INTRODUCTION: Nateglinide or N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine is a drug with a rapid hypoglycemic effect that is mainly used in the treatment of type 2 diabetes. Very few studies have assessed bioequivalence based on feeding status. This study aimed to assess the pharmacokinetic bioequivalence and safety of nateglinide-containing tablets (0.12 g) in healthy Chinese volunteers under fasting and fed conditions. METHODS: The studies were performed in 2017-2018 in the Phase I Clinical Trial Ward of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China. Eligible Chinese volunteers received a single 0.12-g dose of the test or reference formulation, followed by a 7-day washout period and administration of the alternate formulation. Blood samples were collected at various time intervals, and plasma nateglinide concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Then, the adverse events, laboratory test results, vital signs, and physical exam findings were compared between the 2 groups. RESULTS: The ratios of the geometric means of Cmax, AUC0-t, and AUC0-inf of the tested to reference preparations under fasting conditions were 105.03% (90% confidence interval [CI]: 99.53-110.83%), 104.02% (90% CI: 101.37-106.74%), and 104.04% (90% CI: 101.38-106.77%), respectively. The same ratios under fed conditions were 96.55% (90% CI: 85.80-108.65%), 103.08% (90% CI: 100.07-106.18%), and 103.07% (90% CI: 100.21-106.01%), respectively. The 90% CI values for Cmax, AUC0-t, and AUC0-inf fell within the accepted range of bioequivalence (80.00-125.0%). Common adverse events included hypoglycemia, heart rate increase, palpitation, sweating, dizziness, and diarrhea. CONCLUSIONS: The test formulation (0.12 g) met the CFDA's regulatory definition for bioequivalence to the reference formulation. Both formulations were well tolerated by healthy Chinese subjects. TRIAL REGISTRATION: This trial has been registered in the Chinese Clinical trial registry (ChiCTR2000030694), March 10, 2020.

The mechanism of TiaoGanYiPi formula for treating chronic hepatitis B by network pharmacology and molecular docking verification.

The Chinese herbal formula TiaoGanYiPi (TGYP) showed effective against chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection. Hence, we aimed to clarify the mechanisms and potential targets between TGYP and CHB. The active compounds and related putative targets of TGYP, and disease targets of CHB were obtained from the public databases. The key targets between TGYP and CHB were identified through the network construction and module analysis. The expression of the key targets was detected in Gene Expression Omnibus (GEO) dataset and normal hepatocyte cell line LO2. We first obtained 11 key targets which were predominantly enriched in the Cancer, Cell cycle and HBV-related pathways. And the expression of the key targets was related to HBV infection and liver inflammation verified in GSE83148 database. Furthermore, the results of real-time quantitative PCR and CCK-8 assay indicated that TGYP could regulate the expression of key targets including CCNA2, ABL1, CDK4, CDKN1A, IGFR and MAP2K1, and promote proliferation of LO2 cells. In coclusion, we identified the active compounds and key targets btween TGYP and CHB, and found that the TGYP might exhibite curative effect on CHB via promoting hepatocyte proliferation and inhibiting the liver inflammatory processes.

New oxylipins from Siegesbeckia glabrescens as potential antibacterial agents.

Seven rare oxylipins, siegesbeckins A-G (1-7) representing further bioactive constituents different from the general terpenyl compounds found in Siegesbeckia species, have been obtained from the aerial parts of Siegesbeckia glabrescens. These isolates were identified to be a series of methyl 4-methylpentanoates incorporating fatty acid moieties of different chain lengths, based on spectroscopic techniques, and their absolute configurations were determined via chemical degradation and comparison of experimental and theoretically calculated ECD spectra. With respect to bioactivity, antibacterial, anti-inflammatory and cytotoxic properties of selected compounds were evaluated. Compounds 1 and 5 showed moderate antibacterial activity against two Gram-positive bacteria with MIC values of 4.3 µg/mL, while 3 showed no pronounced activity in these assays.

Discovery and identification of antithrombotic chemical markers in Gardenia Fructus by herbal metabolomics and zebrafish model.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia Fructus (GF), a traditional Chinese medicine for clearing heat and purging fire, has been reported to use to treat thrombotic related diseases, but the antithrombotic components are not clear. AIM OF THE STUDY: To develop efficient research methods for discovering some representative antithrombotic compounds of GF. MATERIALS AND METHODS: AB line zebrafish induced by arachidonic acid (AA) was used as a fast and trace-sample-required valuation model for antithrombptic effect of GF samples. Among nine samples of GF from different production areas, two samples with the largest difference in bioactivity were selected for downstream analysis. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was applied to detect compounds in the GF samples. And herbal metabolomics and grey correlation analysis (GCA) were used to identify crucial compounds with potential antithrombotic activity. Then the bioactivity of those important compounds was verified on the zebrafish model. Network pharmacology was used to explore the protein targets and signaling pathways of these compounds. RESULTS: Among the GF samples, S1 (Huoshan City, Anhui Province), and S6 (Jichun City, Hubei Province), significantly differed in thrombus inhibiting bioactivity. HPLC-Q-TOF/MS identified a total of 614 compounds in each GF sample. 19 compounds were selected as important potential variables from metabolomics data by orthogonal partial least squares discriminant analysis (OPLS-DA). And 10 compounds among them were further found to be positively correlated with the antithrombotic bioactivity of GF by GCA. Finally, 3 compounds in them, geniposide, citric acid, and quinic acid, were confirmed as representative antithrombotic chemical markers of GF. Using network pharmacology analysis, some key protein targets, such as proto-oncogene tyrosine-protein kinase Src (SRC) and cyclin-dependent kinase 2 (CDK2), and some signaling pathways were found to supply powerful evidence about antithrombotic mechanisms of three compounds and GF. CONCLUSIONS: This research have succeeded to discover and identify three representative antithrombotic compounds of GF using an efficient integrated research strategy we established, an Omics Discriminant-Grey Correlation-Biological Activity strategy. The antithrombotic chemical makers we found could also contribute to provided more accurate index components for comprehensive quality control of GF.

Investigating the anti-angiogenic effects of Fufang Kushen Injection in combination with cisplatin using a zebrafish model.

The Traditional Chinese Medicine formula Fufang Kushen Injection (FKI) has demonstrated potential to enhance the efficacy and reduce the toxicity of the chemotherapeutic drug cisplatin. However, there is insufficient evidence to determine whether the combination of matrine and cisplatin were linked to the angiogenesis pathway. In this study, we selected two zebrafish lines, AB and Tg (vegfr2: GFP), as in vivo models to rapidly assess the anti-angiogenesis effects. KFI and cisplatin had no obvious effects when used individually, but combined KFI (5 and 10 µL/mL) and cisplatin (50µg/mL) significantly inhibited the zebrafish intersegmental vessel (ISV) formation and growth. Matrine at 50 µg/mL also showed synergetic anti-angiogenesis activity with cisplatin (50µg/mL) in 48hpf zebrafish larvae. This study has shown the potential of FKI to enhance cisplatin efficacy and reduce its toxicity by inhibiting angiogenesis. These results contribute to the scientific evidence supporting the use of KFI in combination with cisplatin to treat cancer in the clinic.

Metabolomics for Biomarker Discovery in Fermented Black Garlic and Potential Bioprotective Responses against Cardiovascular Diseases.

Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.

Comparison of fracture risk using different supplemental doses of vitamin D, calcium or their combination: a network meta-analysis of randomised controlled trials.

OBJECTIVE: Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES: Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS: A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS: The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER: CRD42017079624.

Protective Effect and Mechanisms of New Gelatin on Chemotherapy-Induced Hematopoietic Injury Zebrafish Model.

The aim of the study is to explore the protective effect of new gelatin (NG, Xin'ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 µg·mL-1 and 100 µg·mL-1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.