Evaluation of MASLD Fibrosis, FIB-4 and APRI Score in MASLD Combined with T2DM and MACCEs Receiving SGLT2 Inhibitors Treatment

Hua Liu,1,2,&ast; Yang-Min Hao,1,2,&ast; Sheng Jiang,1,2,&ast; Maiheliya Baihetiyaer,1,2 Cheng Li,3 Guo-Yao Sang,4 Zhiming Li,5 Guo-Li Du1,2,6 1State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Data Statistics and Analysis Center of Operation Management Department, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 4Laboratory Medicine Diagnostic Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 5Department of Ultrasound, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 6Bazhou People’s Hospital, Korla, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Li Du, Email [email protected]: This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs).Methods: A case–control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated.Results: The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P< 0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index.Conclusion: SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.Keywords: MASLD, type 2 diabetes mellitus, sodium-glucose co-transporter-2 inhibitors, MACCEs, FIB-4 inde

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

<p>Abstract</p> <p>Background</p> <p>Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold.</p> <p>Methods</p> <p>The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects.</p> <p>Results</p> <p>Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs.</p> <p>Conclusions</p> <p>To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes.</p

Progenitor-Derivative Relationships of Hordeum Polyploids (Poaceae, Triticeae) Inferred from Sequences of TOPO6, a Nuclear Low-Copy Gene Region

Polyploidization is a major mechanism of speciation in plants. Within the barley genus Hordeum, approximately half of the taxa are polyploids. While for diploid species a good hypothesis of phylogenetic relationships exists, there is little information available for the polyploids (4×, 6×) of Hordeum. Relationships among all 33 diploid and polyploid Hordeum species were analyzed with the low-copy nuclear marker region TOPO6 for 341 Hordeum individuals and eight outgroup species. PCR products were either directly sequenced or cloned and on average 12 clones per individual were included in phylogenetic analyses. In most diploid Hordeum species TOPO6 is probably a single-copy locus. Most sequences found in polyploid individuals phylogenetically cluster together with sequences derived from diploid species and thus allow the identification of parental taxa of polyploids. Four groups of sequences occurring only in polyploid taxa are interpreted as footprints of extinct diploid taxa, which contributed to allopolyploid evolution. Our analysis identifies three key species involved in the evolution of the American polyploids of the genus. (i) All but one of the American tetraploids have a TOPO6 copy originating from the Central Asian diploid H. roshevitzii, the second copy clustering with different American diploid species. (ii) All hexaploid species from the New World have a copy of an extinct close relative of H. californicum and (iii) possess the TOPO6 sequence pattern of tetraploid H. jubatum, each with an additional copy derived from different American diploids. Tetraploid H. bulbosum is an autopolyploid, while the assumed autopolyploid H. brevisubulatum (4×, 6×) was identified as allopolyploid throughout most of its distribution area. The use of a proof-reading DNA polymerase in PCR reduced the proportion of chimerical sequences in polyploids in comparison to Taq polymerase

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd

PI3K and ERK-Induced Rac1 Activation Mediates Hypoxia-Induced HIF-1α Expression in MCF-7 Breast Cancer Cells

Hypoxia-inducible factor 1 (HIF-1α) expression induced by hypoxia plays a critical role in promoting tumor angiogenesis and metastasis. However, the molecular mechanisms underlying the induction of HIF-1α in tumor cells remain unknown.In this study, we reported that hypoxia could induce HIF-1α and VEGF expression accompanied by Rac1 activation in MCF-7 breast cancer cells. Blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1 (T17N) or Rac1 siRNA downregulated hypoxia-induced HIF-1α and VEGF expression. Furthermore, Hypoxia increased PI3K and ERK signaling activity. Both PI3K inhibitor LY294002 and ERK inhibitor U0126 suppressed hypoxia-induced Rac1 activation as well as HIF-1α expression. Moreover, hypoxia treatment resulted in a remarkable production of reactive oxygen species (ROS). N-acetyl-L-cysteine, a scavenger of ROS, inhibited hypoxia-induced ROS generation, PI3K, ERK and Rac1 activation as well as HIF-1α expression.Taken together, our study demonstrated that hypoxia-induced HIF-1α expression involves a cascade of signaling events including ROS generation, activation of PI3K and ERK signaling, and subsequent activation of Rac1

Prediction of Liver-Related Events Using Fibroscan in Chronic Hepatitis B Patients Showing Advanced Liver Fibrosis

Liver stiffness measurement (LSM) using transient elastography (FibroScan®) can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs) in chronic hepatitis B (CHB) patients showing histologically advanced liver fibrosis.Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB) before starting nucleot(s)ide analogues and showed histologically advanced fibrosis (≥F3) with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) and hepatocellular carcinoma (HCC).The mean age of the patient (72 men, 56 women) was 52.2 years. During the median follow-up period [median 27.8 (12.6-61.6) months], LREs developed in 19 (14.8%) patients (five with hepatic decompensation, 13 with HCC, one with both). Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P<0.044; hazard ratio (HR), 1.038; 95% confidence interval (CI), 1.002-1.081]. When the study population was stratified into two groups using the optimal cutoff value (19 kPa), which maximized the sum of sensitivity (61.1%) and specificity (86.2%) from a time-dependent receiver operating characteristic curve, patients with LSM>19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257-22.812; P = 0.001).LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis

Hypoxia Impairs Primordial Germ Cell Migration in Zebrafish (Danio rerio) Embryos

Background: As a global environmental concern, hypoxia is known to be associated with many biological and physiological impairments in aquatic ecosystems. Previous studies have mainly focused on the effect of hypoxia in adult animals. However, the effect of hypoxia and the underlying mechanism of how hypoxia affects embryonic development of aquatic animals remain unclear. Methodology/Principal Findings: In the current study, the effect of hypoxia on primordial germ cell (PGC) migration in zebrafish embryos was investigated. Hypoxic embryos showed PGC migration defect as indicated by the presence of mis-migrated ectopic PGCs. Insulin-like growth factor (IGF) signaling is required for embryonic germ line development. Using real-time PCR, we found that the mRNA expression levels of insulin-like growth factor binding protein (IGFBP-1), an inhibitor of IGF bioactivity, were significantly increased in hypoxic embryos. Morpholino knockdown of IGFBP-1 rescued the PGC migration defect phenotype in hypoxic embryos, suggesting the role of IGFBP-1 in inducing PGC mis-migration. Conclusions/Significance: This study provides novel evidence that hypoxia disrupts PGC migration during embryonic development in fish. IGF signaling is shown to be one of the possible mechanisms for the causal link between hypoxia and PGC migration. We propose that hypoxia causes PGC migration defect by inhibiting IGF signaling through the induction of IGFBP-1