Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence From a Network Meta-Analysis of Randomized Controlled Trials

ObjectiveType 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus.MethodsMedline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness.ResultsA total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): ?6.02%, confidence interval (CI): ?10.37% to ?1.67%] and SGLT2 inhibitors (MD: ?2.60%, CI: ?4.87% to ?0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: ?0.06, CI: ?0.10 to ?0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein.ConclusionGlucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.     

Auxin, Cytokinin and Ethylene Differentially Regulate Specific Developmental States Associated with Shoot Bud Morphogenesis in Leaf Tissues of Mangosteen (Garcinia mangostana L.) Cultured in Vitro

Hormonal regulation of de novo shoot bud formation in leaf explantsof mangosteen has been studied from a developmental perspective.This analysis indicates that at least three discrete, experimentallydistinguishable developmental states, namely, morphogenic competence,caulogenic determination and organ differentiation, were expressedduring shoot bud morphogenesis. The state of morphogenic competencein leaf tissues was expressed maximally between days 10 and12 of leaf development. Competent cells in explants requireda minimum of 6 days of BA treatment (20 µM) to becomecaulogenically determined. Such determined cells would continueshoot organogenesis on medium devoid of growth regulators. Delayingof BA exposure for as short as 2 days caused a dramatic declinein tissue competence. The state of competence and the processof caulogenic determination were adversely affected by IAA,but were insensitive to ethylene or its precursor, ACC. Shootbud differentiation was greatly enhanced by BA, but selectivelydelayed by ethylene. IAA also showed an inhibitory effect onshoot bud differentiation, but not mediated through ethylene.The distinct roles of auxin, cytokinin and ethylene on the regulationof shoot bud development in mangosteen leaf explants have beendiscussed on the basis of the current understanding of the conceptof tissue competence, determination and differentiation. (Received August 12, 1996; Accepted October 31, 1996)     

Effects of nitrogen and sulphur fertilization on the digestibility and chemical composition of perennial ryegrass (Lolium perenne L.)

Summary Effects of increasing rates of nitrogen (N) and sulphur (S) fertilizers on the yield, digestibility, and composition of N, S, and amino acid of perennial ryegrass (Lolium perenne L.) was studied in a pot experiment using an under-developed S-responsive (Harvey) and a developed non-S responsive (Gorge) soil. Ryegrass plants responded significantly to both N and S fertilization in Harvey soil, but only to N and not S in Gorge soil. Digestibility of the herbage was increased by N fertilization and S has no effect. Total N and S concentrations in herbage increased with increasing rates of N and S applied respectively, but decreased with each increment of S and N applied respectively. Total N: total S ratios were highest in high N low S treatments and were consistently decreased by S application, while N application shows the opposite effect. In severely S-deficientplants, unassimilated N accumulated mainly as non-protein N (NPN) (> 40 per cent total N), consisting largely of soluble N compounds (> 90 per cent NPN) such as asparagine/aspartic acid. Under S-sufficiency condition, high N fertilization resulted dominantly in glutamic acid.     

Some observations on surface soil pH,base saturation and leaching of cations under three contrasting orchard soil management practices

Summary Observations from a soil management trial conducted on a previously grassed down orchard showed that after 3 years the pH of the surface soil (0–10 cm) whether measured in distilled water or 1N KCl was significantly lowered in herbicided and cultivated treatments in comparison with plots under continued grass sod. The drop in pH was accompanied by a decrease in base saturation and a consequent increase in exchange acidity. This was attributed to the leaching of Ca and also Mg from the surface soil of the non-grassed plots.In a subsequent laboratory leaching study, cubic soil blocks (16 cm³) were leached with distilled water at two weekly intervals for 24 weeks. It was found that over the experimental period, the cumulative quantity of cations leached (in milli-equivalents) per soil block from the herbicided and cultivated treatments was approximately 3.5 times that leached from the grassed treatment.     

Reference gene selection for normalizing gene expression using quantitative real-time PCR in Haemaphysalis longicornis

The Asian longhorned tick, Haemaphysalis longicornis, the dominant species of Ixodidae in Korea, has a wide distribution in East Asia, far-East Russia, and Western Pacific countries, and has recently been discovered in the Eastern states of the United States of America. H. longicornis transmits various pathogens, including Babesia ovate, Rickettsia japonica, and severe fever with thrombocytopenia syndrome virus (SFTSV). Considering its medical importance, in order to understand the physiology of H. longicornis, it is crucial to determine the expression of the genes of interest. Although quantitative real-time PCR (qRT-PCR) has been widely used to analyze gene expression, stably-expressed internal reference genes across samples of different conditions should be selected for the accurate normalization of target gene expression levels. Therefore, in this study, we investigated the expression levels of five candidate reference genes, namely ACT, RPP0, RPL23, TUB, and GAPDH, in H. longicornis under different conditions, including different collection months, developmental stages, and SFTSV infection status. Using four software programs, namely, NormFinder, BestKeeper, geNorm, and RefFinder, their expression stabilities were evaluated. Subsequently, a single gene between RPL23 and RPP0 was validated, which was found to be most stable reference gene after comparing the expression levels of HSP70 determined using different normalization methods.     

Enrichment of fetal trophoblasts and nucleated erythrocytes from maternal blood by an immunomagnetic colloid system

The aim of this study was to isolate fetal trophoblasts and nucleated erythrocytes from maternal blood using the immunomagnetic colloid system. About 25 ml of maternal blood was collected from pregnant women between of 14 and 20 weeks gestation. Nucleated erythrocytes (NRBCs) were isolated from 5 ml of maternal blood and a nested polymerase chain reaction for the Y chromosome was used to determine fetal origin. The sensitivity of the fetal gender diagnosis was 80% and the specificity was 86%. Both fetal trophoblasts and NRBCs were isolated from the remaining 20 ml of maternal blood. The fetal gender of the trophoblast-enriched fraction was determined using fluorescence in situ hybridisation (FISH) with dual-colour XY-specific DNA probes. XY-specific signals were observed in 0.38% of cells sorted from all pregnant women carrying male fetuses (n = 10). Simultaneous immunophenotyping for the fetal haemoglobin and FISH using XY probes were used to evaluate the fetal origin of cells enriched with anti-CD71. The mean percentage of male fetal erythroblasts was 0.24% and the number of fetal erythroblasts was estimated to be about 672 in 20 ml of maternal blood. The number of fetal erythroblasts detected in our study was greater than that detected by most other separation techniques. Our study shows that it would be feasible to use the immunomagnetic colloid system for the isolation of both trophoblasts and NRBCs from the same maternal blood sample with relatively good efficiency. Received: 17 December 1998 / Accepted: 9 February 1999     

Non-fibrillar amyloid-β peptide reduces NMDA-induced neurotoxicity, but not AMPA-induced neurotoxicity

Amyloid-β peptide (Aβ) is thought to be linked to the pathogenesis of Alzheimer’s disease. Recent studies suggest that Aβ has important physiological roles in addition to its pathological roles. We recently demonstrated that Aβ42 protects hippocampal neurons from glutamate-induced neurotoxicity, but the relationship between Aβ42 assemblies and their neuroprotective effects remains largely unknown. In this study, we prepared non-fibrillar and fibrillar Aβ42 based on the results of the thioflavin T assay, Western blot analysis, and atomic force microscopy, and examined the effects of non-fibrillar and fibrillar Aβ42 on glutamate-induced neurotoxicity. Non-fibrillar Aβ42, but not fibrillar Aβ42, protected hippocampal neurons from glutamate-induced neurotoxicity. Furthermore, non-fibrillar Aβ42 decreased both neurotoxicity and increases in the intracellular Ca²⁺ concentration induced by N-methyl-d-aspartate (NMDA), but not by α-amino-3-hydrozy-5-methyl-4-isoxazole propionic acid (AMPA). Our results suggest that non-fibrillar Aβ42 protects hippocampal neurons from glutamate-induced neurotoxicity through regulation of the NMDA receptor.     

PREDATION BY THE TOXIC DINOFLAGELLATE DINOPHYSIS FORTII ON THE CILIATE MYRIONECTA RUBRA AND OBSERVATION OF SEQUESTRATION OF CILIATE CHLOROPLASTS1

This is the first report of the propagation of the toxic dinoflagellate Dinophysis fortii Pavill. under laboratory conditions when fed on the marine ciliate Myrionecta rubra grown with the cryptophyte Teleaulax amphioxeia (W. Conrad) D. R. A. Hill. In contrast, reduced growth of D. fortii (max. of 3–4 divisions) and formation of small cells were observed in the absence of the ciliate or when provided with T. amphioxeia only as prey, showing that D. fortii cannot utilize T. amphioxeia as prey. In the TEM observation of D. fortii cells, which had fully fed on the ciliate prey, well‐developed chloroplasts (5–12 μm in length) were seen and three thylakoids were usually arranged in most of the chloroplasts observed, but chloroplasts having two thylakoids were sometimes confirmed. In cells starved for 4 weeks, decrease of chloroplast numbers and disappearance of large chloroplasts were observed, and only a few small chloroplasts (0.5–2 μm in length) remained in the marginal regions. In the observation of the sequestration process of the chloroplasts ingested from M. rubra by D. fortii, within 15 min after D. fortii captured M. rubra, incorporation of almost all of the chloroplasts was observed, while most of the other cell contents still remained in the M. rubra cell. After that, dispersion of the ingested chloroplasts toward the marginal regions was confirmed, suggesting that chloroplasts of M. rubra are ingested and dispersed in D. fortii cells in advance of the ingestion of the other cell contents to prevent them from being digested in food vacuoles. The ingested chloroplasts can also function as kleptoplastids.