bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of transferrin glycation induced by high glucose on HK-2 cells in vitro
Authors: Ma Yanqi , Zhou Qikai , Zhao Pingping , Lv Xiaoyu , Gong Caixia , Gao Jie , Liu Jingfang 
Published: January 2023

Background and objectiveGlycation is a common post-transcriptional modification of proteins. Previous studies have shown that advanced glycation end modified transferrin (AGE-Tf) levels in diabetic rat kidney tissues were increased; however, its role in diabetic nephropathy remains unclear. In this study, differences in glycation degree and Tf sites induced by differing high glucose concentrations in vitro and the effect on total iron binding capacity (TIBC) were observed. Moreover, the effect of AGE-Tf on human renal tubular epithelial cells (HK-2) was investigated.MethodsIn vitro Tf was incubated with increasing glucose concentrations (0 mM, 5.6 mM, 11.1 mM, 33.3 mM, 100 mM, 500 mM, and 1,000 mM) for AGE-Tf. Differences in AGE-Tf glycation degree and TIBC level were analyzed via colorimetric method. The AGE-Tf glycation sites were identified with LC-MS/MS. HK-2 cells were treated with AGE-Tf prepared with different glucose concentrations (33.3 mM and 500 mM) in vitro. The effects of AGE-Tf on HK-2 cell viability, proliferation, oxidative stress index, and Tf receptor expression levels were then observed.ResultsWith increasing glucose concentrations (100 mM, 500 mM, and 1,000 mM) in vitro, Tf glycation degree was significantly increased. The TIBC levels of AGE-Tf were decreased significantly with increasing glucose concentrations (33.3 mM, 100 mM, 500 mM, and 1,000 mM). Four glycated modification sites in Tf and 17 glycated modification sites were detected in AGE-Tf (500 mM) by LC-MS/MS. The structural types of AGEs were CML, G-H1, FL-1H2O, FL, and MG-H1. No significant differences were found in the survival rate of HK-2 cells among the AGE-Tf (500 mM), AGE-Tf (33.3 mM), and Tf groups (all p &gt; 0.05). The apoptosis rate of HK-2 cells in the AGE-Tf (500 mM) group was significantly higher than that in the AGE-Tf (33.3 mM) group. Additionally, both of them were significantly higher than that in the Tf group (both p &lt; 0.05). The MDA levels of HK-2 cells in the AGE-Tf (500 mM) and AGE-Tf (33.3 mM) groups were higher than that in the Tf group, but not significantly (both p &gt; 0.05). The T-AOC level of HK-2 in the AGE-Tf (500 mM) group was significantly lower than that in the AGE-Tf (33.3 mM) and Tf groups (both p &lt; 0.001). The GSH level of HK-2 cells in the AGE-Tf (500 mM) group was significantly lower than that in the Tf group (p &lt; 0.05). The expression level of TfR in the AGE-Tf (500 mM) group was also significantly lower than that in the Tf group (p &lt; 0.05).ConclusionThe degree and sites of Tf glycation were increased in vitro secondary to high-glucose exposure; however, the binding ability of Tf to iron decreased gradually. After HK-2 was stimulated by AGE-Tf in vitro, the apoptosis of cells was increased, antioxidant capacity was decreased, and TfR expression levels were downregulated.
Observational assessments of the relationship of dietary and pharmacological treatment on continuous measures of dysglycemia over 24 hours in women with gestational diabetes
Authors: Dingena Cassy F. , Holmes Melvin J. , Campbell Matthew D. , Cade Janet E. , Scott Eleanor M. , Zulyniak Michael A. 
Published: January 2023

ObjectivesStudies that use continuous glucose monitoring (CGM) to monitor women with gestational diabetes (GDM), highlight the importance of managing dysglycemia over a 24-hour period. However, the effect of current treatment methods on dysglycemia over 24-hrs are currently unknown. This study aimed to characterise CGM metrics over 24-hrs in women with GDM and the moderating effect of treatment strategy.MethodsRetrospective analysis of CGM data from 128 women with GDM in antenatal diabetes clinics. CGM was measured for 7-days between 30-32 weeks gestation. Non-parametric tests were used to evaluate differences of CGM between periods of day (morning, afternoon, evening, and overnight) and between treatment methods (i.e., diet alone or diet+metformin). Exploratory analysis in a subgroup of 34 of participants was performed to investigate the association between self-reported macronutrient intake and glycaemic control.ResultsGlucose levels significantly differed during the day (i.e., morning to evening; P&lt;0.001) and were significantly higher (i.e., mean blood glucose and area under the curve [AUC]) and more variable (i.e., SD and CV) than overnight glucose levels. Morning showed the highest amount of variability (CV; 8.4% vs 6.5%, P&lt;0.001 and SD; 0.49 mmol/L vs 0.38 mmol/L, P&lt;0.001). When comparing treatment methods, mean glucose (6.09 vs 5.65 mmol/L; P&lt;0.001) and AUC (8760.8 vs 8115.1 mmol/L.hr; P&lt;0.001) were significantly higher in diet+metformin compared to diet alone. Finally, the exploratory analysis revealed a favourable association between higher protein intake (+1SD or +92 kcal/day) and lower mean glucose (-0.91 mmol/L p, P=0.02) and total AUC (1209.6 mmol/L.h, P=0.021).ConclusionsGlycemia varies considerably across a day, with morning glycemia demonstrating greatest variability. Additionally, our work supports that individuals assigned to diet+metformin have greater difficulty managing glycemia and results suggest that increased dietary protein may assist with management of dysglycemia. Future work is needed to investigate the benefit of increased protein intake on management of dysglycemia.
The serum follicle stimulating hormone-to-luteinizing hormone ratios can predict assisted reproductive technology outcomes in women undergoing gonadotropin releasing hormone antagonist protocol
Authors: Zhao Shen , Xu Huihui , Wu Xian , Xia Lan , Li Jian , Zhang Dan , Zhang Aijun , Xu Bufang 
Published: January 2023

BackgroundThe basal follicle stimulating hormone (FSH)/luteinizing hormone (LH) ratio is a useful predictor of ovarian response. In this study, we investigated whether the FSH/LH ratios during the entire controlled ovarian stimulation (COS) can be used as effective predictors of outcomes in women undergoing in vitro fertilization (IVF) treatment using the gonadotropin releasing hormone antagonist (GnRH-ant) protocol.MethodsA total of 1,681 women undergoing their first GnRH-ant protocol were enrolled in this retrospective cohort study. A Poisson regression model was used to analyze the association between the FSH/LH ratios during COS and embryological outcomes. Receiver operating characteristic analysis was performed to determine the optimal cutoff values for poor responders (≤ 5 oocytes) or poor reproductive potential (≤ 3 available embryos). A nomogram model was constructed to provide a tool for predicting the cycle outcomes of individual IVF treatments.ResultsThe FSH/LH ratios (at the basal day, stimulation day 6 (SD6) and trigger day) were significantly correlated with the embryological outcomes. The basal FSH/LH ratio was the most reliable predictor of poor responders with a cutoff value of 1.875 (area under the curve (AUC) = 72.3%, P &lt; 0.05), or of poor reproductive potential with a cutoff value of 2.515 (AUC = 66.3%, P &lt; 0.05). The SD6 FSH/LH ratio predicted poor reproductive potential with a cutoff value of 4.14 (AUC = 63.8%, P &lt; 0.05). The trigger day FSH/LH ratio predicted poor responders with a cutoff value of 9.665 (AUC = 63.1%, P &lt; 0.05). The basal FSH/LH ratio, combined with the SD6 and trigger day FSH/LH ratios, slightly increased these AUC values and improved the prediction sensitivity. The nomogram provides a reliable model with which to assess the risk of poor response or poor reproductive potential directly based on the combined indicators.ConclusionsFSH/LH ratios are useful predictors of poor ovarian response or reproductive potential throughout the entire COS with the GnRH antagonist protocol. Our findings also provide insights into the potential for LH supplementation and regimen adjustment during COS to achieve improved outcomes.
Factors associated with gastrointestinal side effects after liraglutide treatment for type 2 diabetes
Authors: Wu Hao , Lu Zongshi , Chen Runyao , Cai Quanfang , Wang Miaomiao , Zhang Liting , Zhu Zhiming 
Published: January 2023

AimTo identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM).MethodsT2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values.ResultsA total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p &lt;0.05). In the final regression model, AGI use (adjusted OR=4.01, 95%CI: 1.90-8.45, p&lt;0.001), gastrointestinal diseases (adjusted OR=3.29, 95%CI: 1.51-7.18, p=0.003), TSH (adjusted OR=1.79, 95%CI: 1.28-2.50, p=0.001) and male sex (adjusted OR=0.19, 95%CI: 0.10-0.37, p&lt;0.001) were independently associated with GSEA. Furthermore, ROC curve analysis confirmed that TSH values of 1.33 and 2.30 in females and males, respectively, were useful thresholds for predicting GSEA.ConclusionThis study suggests that the combination of AGI, concomitant gastrointestinal diseases, female sex and higher TSH levels are independent risk factors of GSEA of liraglutide treatment in patients with T2DM. Further research is warranted to elucidate these interactions.
Cardiorespiratory fitness in adolescents and young adults with Klinefelter syndrome – a pilot study
Authors: Spiekermann Julia , Sinningen Kathrin , Hanusch Beatrice , Kleber Michaela , Schündeln Michael M. , Kiewert Cordula , Siggelkow Heide , Höppner Jakob , Grasemann Corinna 
Published: January 2023

BackgroundKlinefelter syndrome (KS) may be associated with a wide spectrum of phenotypic changes including endocrine, metabolic, cognitive, psychiatric and cardiorespiratory pathologies in adults. However, in adolescence the clinical phenotype of KS is not well described, especially regarding physical fitness. The present study reports on cardiorespiratory function in adolescents and young adults with KS.MethodsAdolescents and young adults with KS were recruited in a cross-sectional pilot study. Biochemical parameters of fitness including hormonal status, a body impedance analysis, the grip strength, the amount of physical activity at home for 5 days via trackbands and anamnestic parameters were assessed. In addition, participants underwent an incremental symptom-limited cardiopulmonary exercise test (CPET) on a bicycle ergometer.ResultsNineteen participants with KS aged 15.90 ± 4.12 years (range: 9.00 - 25.00) participated in the study. Pubertal status was Tanner 1 (n = 2), Tanner 2 - 4 (n = 7) and Tanner 5 (n = 10). Seven participants received testosterone replacement therapy. Mean BMI z-score was 0.45 ± 1.36 and mean fat mass was 22.93% ± 9.09. Grip strength was age-appropriate or above normal. 18 participants underwent CPET with subnormal results for maximum heart rate (z-score -2.84 ± 2.04); maximum workload (Wattmax; z score -1.28 ± 1.15) and maximum oxygen uptake per minute (z- score -2.25 ± 2.46). Eight participants (42.1%) met the criteria for chronotropic insufficiency (CI). Data from track-bands showed sedentary behavior for 81.15% ± 6.72 of the wear time.ConclusionA substantial impairment of cardiopulmonary function can be detected in this group of boys to young adults with KS, including chronotropic insufficiency in 40%. The track-band data suggest a predominantly sedentary lifestyle, despite normal muscular strength as assessed via grip strength. Future studies need to investigate the cardiorespiratory system and its adaption to physical stress in a larger cohort and in more detail. It is feasible that the observed impairments contribute to the avoidance of sports in individuals with KS and may contribute to the development of obesity and the unfavorable metabolic phenotype.
Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies
Authors: Dehdari Ebrahimi Niloofar , Parsa Shima , Nozari Farnoosh , Shahlaee Mohammad Amin , Maktabi Amirhossein , Sayadi Mehrab , Sadeghi Alireza , Azarpira Negar 
Published: January 2023

BackgroundEnvironmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials.MethodsA systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy’s effects on rodents’ testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872)ResultsOut of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains.ConclusionIn conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.
A novel pyroptosis gene expression-based risk score for survival in gastric cancer
Authors: Hu Jiali , Song Yang , Cai Xintian , Halina Halike , Qiao Kun , Lu Jiajie , Yin Chengliang , Gao Feng 
Published: January 2023

BackgroundGastric cancer (GC) is a highly heterogeneous disease, which makes treatment and prognosis prediction difficult. Pyroptosis plays a vital role in the development of GC and influence the prognosis of GC. Long non-coding RNAs (lncRNAs), as regulators of gene expressions, are among putative biomarkers and therapeutic targets. However, the importance of pyroptosis-associated lncRNAs is still unclear in predicting prognosis in gastric cancer.MethodsIn this study, the mRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. A pyroptosis-related lncRNA signature was constructed based on TCGA databases by using the Least Absolute Shrinkage and Selection Operator (LASSO) method Cox regression model. GC patients from the GSE62254 database cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent predictors for OS. Gene set enrichment analyses were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT.ResultsA four-pyroptosis-related lncRNA (ACVR2B-AS1, PRSS30P, ATP2B1-AS1, RMRP) signature was constructed using LASSO Cox regression analysis. GC patients were stratified into high- and low-risk groups, and patients in the high-risk group showed significant worse prognosis in TNM stage, gender, and age. The risk score was an independent predictor for OS by multivariate Cox analysis. Functional analysis indicated that the immune cell infiltrate was different between high- and low-risk groups.ConclusionThe pyroptosis-related lncRNA prognostic signature can be used for predicting prognosis in GC. Moreover, the novel signature might provide clinical therapeutic intervention for GC patients.
Expression profiles of lncRNAs and their possible regulatory role in monocrotaline-induced HSOS in rats
Authors: Ismail Mohammed , Zhang Xi , Taha Reham , Elhafiz Muhanad , Zhang Qianwen , Yousef Bashir A. , Huang Xin , Jiang Zhenzhou , Zhang Luyong , Sun Lixin 
Published: January 2023

Aims: Long non-coding RNAs (lncRNAs) contribute to the regulation of vital physiological processes and play a role in the pathogenesis of many diseases. Monocrotaline (MCT) can cause large-scale outbreaks of toxic liver disease in humans and animals in the form of hepatic sinusoidal obstruction syndrome (HSOS). Although many experiments have been carried out to explain the pathogenesis of Monocrotaline-induced hepatic sinusoidal obstruction syndrome and to develop treatments for it, no studies have examined the role of Long non-coding RNAs in this condition. This study aimed to investigate the Long non-coding RNAs–mRNA regulation network in Monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats.Main methods: We established a model for MCT-induced hepatic sinusoidal obstruction syndrome, and then carried out microarray for liver tissues of SD rats in a model of early hepatic sinusoidal obstruction syndrome (12 h Monocrotaline treatment vs. control group) to investigate the differentially expressed Long non-coding RNAs and mRNAs in early hepatotoxicity. This was followed by RT-PCR analysis of selected Long non-coding RNAs, which were markedly altered. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome analyses were also conducted.Key findings: 176 Long non-coding RNAs (63 downregulated and 113 upregulated) and 4,221 mRNAs (2,385 downregulated and 1836 upregulated) were differentially expressed in the Monocrotaline-treated group compared to the control group. The biological processes identified in GO enrichment analysis as playing a role in hepatotoxicity were positive regulation of guanosine triphosphate phosphohydrolase, liver development, and the oxidation-reduction process. Pathway analysis revealed that the metabolism pathways, gap junction, and ribosome biogenesis in eukaryotes were closely related to Monocrotaline-induced hepatotoxicity. According to these analyses, LOC102552718 might play an essential role in hepatotoxicity mechanisms by regulating the expression of inositol 1,4,5-trisphosphate receptor-1 (Itpr-1).Significance: This study provides a basis for further research on the molecular mechanisms underlying Monocrotaline-induced hepatotoxicity and its treatment, especially in the early stage, when successful treatment is critical before irreversible liver damage occurs.
A combination of the HLA-DRB1*03 phenotype and low plasma mannose-binding lectin predisposes to autoantibody formation in women with recurrent pregnancy loss
Authors: Nørgaard-Pedersen Caroline , Steffensen Rudi , Kesmodel Ulrik Schiøler , Christiansen Ole Bjarne 
Published: January 2023

IntroductionIt is documented that a series of autoantibodies can be detected with increased frequency in women with recurrent pregnancy loss (RPL) and they may impact the pregnancy prognosis negatively. It is unknown whether the autoantibodies per se or the basic immune disturbances underlying autoantibody production, are the reason for this association. Our group has previously found that some genetically determined immunological biomarkers are associated with RPL and the same biomarkers are also in various degrees known to predispose to autoantibody production. The aim of this study was to clarify whether the RPL-associated immunogenetic biomarkers are associated with positivity for three major classes of autoantibodies associated with RPL.MethodsIn 663 patients with RPL in whom we had results for HLA-DRB1 typing and plasma mannose-binding lectin (p-MBL) measurement, it was investigated whether there is a correlation between positivity for the autoantibodies: anticardiolipin antibodies, β2 glycoprotein I antibodies, and lupus anticoagulant (jointly called antiphospholipid antibodies), thyroid-peroxidase antibodies, and antinuclear antibodies and each of the HLA-DRB1 alleles HLA-DRB1*03 or HLA-DRB1*07 either alone or in combination with low p-MBL defined as ≤500 µg/l.ResultsAlthough slightly higher frequencies of positivity of two or more autoantibodies were seen in patients with either p-MBL ≤500 µg/l or being positive for HLA-DRB1*03, none were significantly associated. However, in patients with the combination of low p-MBL and HLA-DRB1*03, presence of at least one autoantibody was significantly more frequent than in patients with no such combination (OR= 2.4; 95% CI 1.2-5.0, p = 0.01). In an analysis of which autoantibodies were most strongly associated with the low p-MBL/HLA-DRB1*03 combination, antinuclear antibodies were significantly more frequent in these patients (OR 2.0; 95% CI 1.0-3.9, p=0.05) whereas the other autoantibodies were also positively but more weakly associated with this combination.DiscussionIn conclusion, to clarify the pathogenetic background, underlying immunogenetic factors should be examined in autoantibody positive RPL patients (as well as other patients with autoimmune diseases) but the genetic background may be complex.