Physiology of the ECL cells.

The enterochromaffin-like (ECL) cells of the oxyntic mucosa (fundus) of the stomach produce, store and secrete histamine, chromogranin A-derived peptides such as pancreastatin, and an unanticipated but as yet unidentified peptide hormone. The cells are stimulated by gastrin and pituitary adenylate cyclase activating peptide and suppressed by somatostatin and galanin. Choline esters and histamine seem to be without effect on ECL cell secretion. The existence of a gastrin-ECL cell axis not only explains how gastrin stimulates acid secretion but also may help to explore the functional significance of the ECL cells with respect to the nature and bioactivity of its peptide hormone. From the results of studies of gastrectomized/fundectomized and gastrin-treated rats, it has been speculated that the anticipated ECL-cell peptide hormone acts on bone metabolism.     

Functions and mechanisms of plant histone deacetylases

Lysine acetylation, one of the major types of post-translational modifications, plays critical roles in regulating gene expression and protein function. Histone deacetylases(HDACs) are responsible for removing acetyl groups from lysines of both histone and non-histone proteins. While tremendous progress has been made in understanding the function and mechanism of HDACs in animals in the past two decades, nearly half of the HDAC studies in plants were reported within the past five years. In this review,we summarize the major findings on plant HDACs, with a focus on the model plant Arabidopsis thaliana, and highlight the components, regulatory mechanisms, and biological functions of HDAC complexes.     

Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng

Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The K_m and V_max values of CK were 84.20±21.92 μM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 μM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 μM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC₅₀ values were 16.00 μM and 9.83 μM, and K_i values were 14.92 μM and 11.42μM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors.     

A High-Order,Symplectic, Finite-Difference Time-Domain Scheme for Bioelectromagnetic Applications within the Mother/Fetus Model

An explicit high-order, symplectic, finite-difference time-domain (SFDTD) scheme is applied to a bioelectromagnetic simulation using a simple model of a pregnant woman and her fetus. Compared to the traditional FDTD scheme, this scheme maintains the inherent nature of the Hamilton system and ensures energy conservation numerically and a high precision. The SFDTD scheme is used to predict the specific absorption rate (SAR) for a simple model of a pregnant female woman (month 9) using radio frequency (RF) fields from 1.5 T and 3 T MRI systems (operating at approximately 64 and 128 MHz, respectively). The results suggest that by using a plasma protective layer under the 1.5 T MRI system, the SAR values for the pregnant woman and her fetus are significantly reduced. Additionally, for a 90 degree plasma protective layer, the SAR values are approximately equal to the 120 degree layer and the 180 degree layer, and it is reduced relative to the 60 degree layer. This proves that using a 90 degree plasma protective layer is the most effective and economical angle to use.     

α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.     

The Role of Host Cytoskeleton in Flavivirus Infection

The family of flaviviruses is one of the most medically important groups of emerging arthropod-borne viruses. Host cell cytoskeletons have been reported to have close contact with flaviviruses during virus entry, intracellular transport, replication, and egress process, although many detailed mechanisms are still unclear. This article provides a brief overview of the function of the most prominent flaviviruses-induced or-hijacked cytoskeletal structures including actin, microtubules and intermediate filaments, mainly focus on infection by dengue virus, Zika virus and West Nile virus. We suggest that virus interaction with host cytoskeleton to be an interesting area of future research.     

Correction of chromosomal point mutations in human cells with bifunctional oligonucleotides.

A sequence-specific genomic delivery system for the correction of chromosomal mutations was designed by incorporating two different binding domains into a single-stranded oligonucleotide. A repair domain (RD) contained the native sequence of the target region. A third strand-forming domain (TFD) was designed to form a triplex by Hoogsteen interactions. The design was based upon the premise that the RD will rapidly form a heteroduplex that is anchored synergistically by the TFD. Deoxyoligonucleotides were designed to form triplexes in the human adenosine deaminase (ADA) and p53 genes adjacent to known point mutations. Transfection of ADA-deficient human lymphocytes corrected the mutant sequence in 1-2% of cells. Neither the RD or TFD individually corrected the mutation. Transfection of p53 mutant human glioblastoma cells corrected the mutation and induced apoptosis in 7.5% of cells.