Oral consumption of α-glucosyl-hesperidin could prevent lens hardening,which causes presbyopia

Presbyopia is one of the most well-known diseases of the eye, predominantly affecting the adult population after 50 years’. Due to hardening of the lens and failure of accommodative change, patients lose the ability to focus on near objects. This eye symptom is reported to be an early symptom of age-related nuclear cataract, and we have previously reported that hesperetin treatment could delay the onset of nuclear cataractogenesis induced by sodium selenite. In this study, we examined whether oral intake of α-glucosyl-hesperidin (G-Hsd), which has greater water solubility than hesperetin, could delay the onset of presbyopia. G-Hsd treatment protected lens elasticity, upregulated the mRNA expression of anti-oxidative enzymes like glutathione reductase and thioredoxin reductase 1 in the plasma and lens, and prevented premature cataract symptoms in selenite-induced cataract rat lens. Thus, the anti-presbyopic effects of G-Hsd were attributed, at least in part, to its antioxidant effects. G-Hsd represents the first oral treatment agent with anti-presbyopia and/or anti-cataract properties.     

Ultrastructural changes of renal tubules in the riboflavin deficient mouse

Ultrastructural changes of the tubular epithelium in the mouse kidney produced by dietary riboflavin deficiency were studied by electron microscopy and cytochemistry. In riboflavin deficient mouse kidney, the ultrastructural changes are localized to the pars recta of the proximal tubule. They comprise so called vacuolar degeneration on light microscopy, which consists of the formation of giant mitochondria and vacuoles. During the development of riboflavin deficiency, mitochondria decrease in number and enlarge in size through fusion. Sometimes they are larger than nuclei in size. The vacuoles observed in tubular epithelia are divided into two different groups according to their morphological characteristics and origins. One is derived from proliferated peroxisomes, and another from increased cytoplasmic bodies termed cytosomes and cytosegresomes. These increased vacuoles occupy almost all of cytoplasm. Cytochemical studies also reveal that these vacuoles are peroxisomes and lysosomes. These changes are reversible on supplementation with riboflavin.     

The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses

HIV-1 CRF01_AE viruses are highly prevalent in Southeast Asia. However, vulnerability sites in Env of CRF01_AE viruses have not been investigated sufficiently. We examined the sensitivity of CRF01_AE viruses from Japan and Vietnam, together with subtype B viruses from Japan, to neutralization and Fc-mediated signaling. Neutralization coverage of broadly neutralizing antibodies (bnAbs), 2G12 and b12, was significantly low against CRF01_AE viruses, compared with subtype B viruses. In contrast, the conventional antibody targeting the CD4 binding site (CD4bs), 49G2, showed better neutralization and Fc-mediated signaling activities against CRF01_AE viruses than subtype B viruses. Fc-mediated signaling activity of anti-CD4 induced (CD4i) antibody, 4E9C, was also detected against CRF01_AE viruses more than subtype B viruses. These results suggest that conventional antibodies against CD4bs and CD4i may play an important role in the control of CRF01_AE viruses.     

Syntheses of prodrug-type phosphotriester oligonucleotides responsive to intracellular reducing environment for improvement of cell membrane permeability and nuclease resistance

We synthesized prodrug-type phosphotriester (PTE) oligonucleotides containing the six-membered cyclic disulfide moiety by using phosphoramidite chemistry. Prodrug-type oligonucleotides named “Reducing-Environment-Dependent Uncatalyzed Chemical Transforming (REDUCT) PTE oligonucleotides” were converted into natural oligonucleotides under cytosol-mimetic reductive condition. Furthermore, the REDUCT PTE oligonucleotides were robust to nuclease digestion and exhibited good cell membrane permeability.     

Isoproterenol potentiates alpha -adrenergic and muscarinic receptor-mediated Ca2+ response in rat parotid cells

The effects of the cAMP pathway on theCa²⁺ response elicited byphospholipase C-coupled receptor stimulations were studied in ratparotid cells. Although 1 µM isoproterenol (Iso) itself had no effect on the cytosolicCa²⁺ concentration, thepretreatment with Iso potentiatedCa²⁺ responses evoked byphenylephrine. The potentiating effect of Iso was attributed to ashifting of the concentration-response curves of phenylephrine to theleft and an increase in the maximal response. Half-maximal potentiationoccurred at 3 nM Iso. Iso also potentiated theCa²⁺ response elicited bycarbachol. The potentiating effect of Iso was mimicked by forskolin (10 µM) and dibutyryl adenosine 3',5'-cyclic monophosphate (2 mM) and was blocked by 10 µM H-89. Iso potentiated thephenylephrine-induced Ca²⁺response in the absence of extracellularCa²⁺, but Iso did not increase theinositol trisphosphate (IP₃)production induced by phenylephrine. These results suggest that thepotentiation of the Ca²⁺ responsecan be attributed to a sensitization ofIP₃ receptors by cAMP-dependentprotein kinase.

     

Human mesor-hypertensive chronorisk

Twelve endocrine variables in blood from a small number of clinically healthy adult women were sampled systematically around the clock and the seasons. Pattern discrimination methods singled out certain hormone values in certain seasons as classifiers for a high vs low risk of developing diseases associated with a high blood pressure. Further evidence in support of such classifiers is obtained on data from adolescent, menstrually cycling young adults and post-menopausal women, here analyzed as pool of series, with the scope of the data from any one age group greatly extended by a resampling procedure, namely, by bootstrapping. This mathematical approach was carried out on data series around the clock and seasons on several hormones as well as systolic and diastolic blood pressure. Classifier roles were strongly supported for plasma aldosterone and thyroid stimulating hormone, originally by an analysis of variance and, in the case of aldosterone, by circannual cosinor analysis and by numerical resampling. Circannual bootstrapping, a procedure recommended for broad routine use as a safeguard for hypothesis testing, was also done for plasma cortisol, dehydro-epi-androsterone sulfate and prolactin, variables for which (parametric) analyses of variance and cosinors did not reveal any difference between groups at high and low cardiovascular risk. In these instances, bootstrapping results are tentative and await further analyses. Results show the ability of circannual bootstrapping to detect outliers. Identification of classifiers provides cost-effective endocrine checks complementing the targeted automatic monitoring of blood pressure. Circannual indices for risk evaluation are, however, costly in several ways since it takes at least a year and quite a few samples to estimate them reliably. Accordingly, we also extended the scope of previous results by the application of an added procedure for circadian bootstrapping. With circadian as well as circannual bootstrapping, we here illustrate a major potential component of a system of chrono-engineering for health maintenance. This system should start with focus on the newborn. The results on adults here analyzed are likely to be more prominent in the neonate, to the extent that they are genetic in origin, yet amenable to modification by the extra-uterine environment.     

Tetraether type polar lipids increase after logarithmic growth phase of Methanobacterium thermoautotrophicum in compensation for the decrease of diether lipids

Abstract The ratios of tetraether to diether type lipids in the total lipid during cell growth in batch cultures of Methanobacterium thermoautotrophicum ΔH (DSM 1053) were examined. The proportion of tetraether type lipids to the total lipid was about 80% during the log phase, and at the onset of the transient phase it began to rise up to about 93%. It was kept almost constant at that level throughout the stationary phase. The polar lipid composition changed with the age of the cell culture. The proportions of all the diether type polar lipids were lower and the levels of all tetraether type polar lipids were higher in the stationary phase than in the log phase. On the other hand, the composition of polar head groups, irrespective of the core lipids, was nearly constant in both growth phases measured so far despite the change in core lipid composition.