Effects of ß-carotene supplementation in the diet of laying breeder hens on the growth performance and liver development of offspring chicks.

This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.

Bigelovin inhibits hepatocellular carcinoma cell growth and metastasis by regulating the MAPT-mediated Fas/FasL pathway.

Bigelovin (BigV), as traditional Chinese medicine, has been shown to inhibit the malignant progression of hepatocellular carcinoma (HCC). This study aimed to investigate whether BigV affects the development of HCC by targeting the MAPT and Fas/FasL pathway. Human HCC cell lines HepG2 and SMMC-7721 were used for this study. Cells were treated with BigV, sh-MAPT, and MAPT. The viability, migration, and apoptosis of HCC cells were detected by CCK-8, Transwell, and flow cytometry assays, respectively. Immunofluorescence and immunoprecipitation were used to verify the relationship between MAPT and Fas. Subcutaneous xenograft tumor and tail vein-injected lung metastases mouse models were constructed for histological observation. Hematoxylin-eosin staining was used to assess lung metastases in HCC. Western blotting was used to measure the expression of migration, apoptosis, and epithelial-mesenchymal transition (EMT) marker proteins, as well as Fas/FasL pathway-related proteins. BigV treatment inhibited the proliferation, migration, and EMT of HCC cells, whereas enhanced cell apoptosis. Moreover, BigV downregulated MAPT expression. The negative effects of sh-MAPT on HCC cell proliferation, migration, and EMT were enhanced by BigV treatment. Conversely, BigV addition attenuated the positive effects of MAPT overexpression on the malignant progression of HCC. In vivo experiments showed that BigV and/or sh-MAPT reduced tumor growth and lung metastasis while promoting tumor cell apoptosis. Furthermore, MAPT could act with Fas and inhibit its expression. sh-MAPT upregulated the expression of Fas/FasL pathway-associated proteins, which were enhanced by BigV administration. BigV suppressed the malignant progression of HCC via activating the MAPT-mediated Fas/FasL pathway.

Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials.

Introduction: Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women. Methods: We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria. Results: Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) (P = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 (P = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, P = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, P = 0.76). Conclusions: The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.

Platelet-Facilitated Photothermal Therapy of Head and Neck Squamous Cell Carcinoma.

Here, we present a platelet-facilitated photothermal tumor therapy (PLT-PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR-loaded PLTs (PLT-AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene-knockout mouse model, we demonstrate that the administration of PLT-AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT-AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self-reinforcing characteristic of PLT-PTT in cancer therapy.

New abietane-type diterpene glycosides from the roots of Tripterygium wilfordii.

Two new abietane diterpene glycosides, wilfordosides A (1) and B (2), were isolated from the roots of Tripterygium wilfordii. The structures of compounds 1 and 2 were established using spectroscopic methods including extensive 1D and 2D NMR analysis, in combination with chemical reactions.

Establishment of a yeast system that stably expresses human cytochrome P450 reductase: application for the study of drug metabolism of cytochrome P450s in vitro.

Cytochrome P450s (CYPs) hold a balance in studying pharmacokinetics, toxico-kinetics, drug metabolism, and drug-drug interactions, which require association with cytochrome P450 reductase (CPR) to achieve optimal activity. A novel system of Saccharomyces cerevisiae useful for expression studies of mammalian microsomal CYPs was established. Human CPR (hCPR) was co-expressed with human CYP3A4 (hCYP3A4) in this system, and two expression plasmids pTpLC and pYeplac195-3A4 containing the cDNA of hCPR and hCYP3A4 were constructed, respectively. The two plasmids were applied first and controlled by phosphoglycerate kinase (PGK) promoter. S. cerevisiae BWG1-7alpha transformed with the expression plasmids produced the respective proteins in the expected molecular sizes reactive with both anti-hCYP3A4 immunoglobulin (Ig) and anti-hCPR Ig. The activity of hCPR in yeast BWG-CPR was 443.2 nmol reduced cytochrome c/min/mg, which was about three times the CPR activity of the microsome prepared from the parental yeast. The protein amount of hCYP3A4 in BWG-CPR/3A4 was 35.53 pmol/mg, and the 6beta-hydroxylation testosterone formation activity of hCYP3A4 expressed was 7.5 nmol/min/nmol CYP, 30 times higher than the activity of hCYP3A4 expressed in the parental yeast, and almost two times the activity of hCYP3A4 from homologous human liver microsome. Meanwhile, BWG-CPR/3A4 retained 100 generations under nonselective culture conditions, indicating this yeast was a mitotically stable transformant. BWG-CPR was further tested daily by the PCR amplification of hCPR of yeast genome, Western blot analysis, and the activity assay of hCPR of yeast microsome. This special expression host for CYPs was validated to be stable and efficient for the expression of CYPs, applying as an effective selection model for the drug metabolism in vitro.