Metabolism describes the series of chemical reactions that are concerned with the provision of energy to biological systems. They may be divided into reactions involved in energy yield (catabolism: demand exceeds supply), and energy storage (anabolism: supply exceeds demand). Regulation of these pathways is critical for homeostasis, and derangements in metabolism are seen in a wide variety of pathological processes. Understanding metabolism is key to the treatment of many diseases, notably diabetes, as well as underpinning clinical nutritional support. 相似文献
Preimplantation genetic diagnosis (PGD) was originally developed to diagnose
embryo-related genetic abnormalities for couples who present a high risk of a
specific inherited disorder. Because this technology involves embryo selection, the
medical, bioethical, and legal implications of the technique have been debated,
particularly when it is used to select features that are not related to serious
diseases. Although several initiatives have attempted to achieve regulatory
harmonization, the diversity of healthcare services available and the presence of
cultural differences have hampered attempts to achieve this goal. Thus, in different
countries, the provision of PGD and regulatory frameworks reflect the perceptions of
scientific groups, legislators, and society regarding this technology. In Brazil,
several texts have been analyzed by the National Congress to regulate the use of
assisted reproduction technologies. Legislative debates, however, are not conclusive,
and limited information has been published on how PGD is specifically regulated. The
country requires the development of new regulatory standards to ensure adequate
access to this technology and to guarantee its safe practice. This study examined
official documents published on PGD regulation in Brazil and demonstrated how little
direct oversight of PGD currently exists. It provides relevant information to
encourage reflection on a particular regulation model in a Brazilian context, and
should serve as part of the basis to enable further reform of the clinical practice
of PGD in the country. 相似文献
AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain. 相似文献
1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献
Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?.001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5–10.5?mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD. 相似文献
The presence of pesticides in the Israeli food supply is well documented but little is known about the risks posed by children's diets for potential exposures. We investigated potential exposures to food-borne pesticides in a sample of 301 urban Israeli children (2008–10). Data from a food frequency questionnaire, 24 hour food recall, and Israel's national pesticide monitoring program were used to estimate uptake factors for 26 compounds in 27 fruits and vegetables. A pilot risk assessment was performed and the findings were compared with the Israel Ministry of Health's 2012 pesticide risk assessment for the general population. The surveyed children had higher potential exposures than the general population for over one third of the compounds, and uptake factors exceeded the Acceptable Daily Intake in ten compounds. Methamidophos, exceeded the ADI at the 25th percentile and fenamiphos, iprodione, and oxydemethon methyl, exceeded the ADI at the 50 percentile. ADIs for several compounds were exceeded even though the residues detected were below the statutory limit. Improved monitoring, enforcement, and revision of the Maximum Residue Limit for certain food/pesticide pairs are indicated as is the need to incorporate data on children's actual food consumption in national risk assessments. 相似文献