bluuebunny/crossref_metadata_2025 huggingface dataset:
The feasibility of small-caliber veins for autogenous arteriovenous fistula creation: A single-center retrospective study
Authors: Feng Ruijia , Wang Siwen , Chang Guangqi , Zhang Wayne W. , Liu Qinghua , Wang Xin , Chen Wei , Wang Shenming
Published: January 2023

Objective

Autogenous arteriovenous fistula (AVF) is recommended as the first choice for hemodialysis vascular access. A small-caliber vein is one of the independent risk factors for AVF maturation and patency. However, the specific threshold is still unclear, making it difficult to accurately determine whether these vessels are suitable for AVF creation.

Design

This is a single-center retrospective study.

Method

Patients who underwent AVF creation in our medical center between January 2020 and September 2022 and satisfied the eligibility criteria were included in this retrospective study. Logistic regression analysis was performed to identify risk factors for functional maturation and additional intervention. The optimal cutoff value was determined based on the receiver operating curve (ROC) and the Youden index. Kaplan–Meier analysis was utilized in further patency rate comparisons.

Result

A total of 125 forearm AVFs were created in 121 patients with end-stage renal disease (ESRD). The mean age was 53.88 ± 15.10  years. Preoperative vascular Doppler ultrasound (DUS) was conducted and recorded in 106 cases (84.80%). The mean targeted artery and vein diameters were 2.17 ± 0.54 and 1.71 ± 0.75  mm, respectively. Small-caliber vein is the risk factor for functional maturation failure (OR = 0.256, 95%CI [0.06–0.75], p = 0.033) and additional intervention (OR = 0.306, 95% CI [0.09–0.78], p = 0.031). The optimal cutoff value is 1.35  mm (augmented) when specificity and sensitivity reach 80 and 63.7%, respectively. The AVFs with a vein diameter of more than 1.35 mm (augmented) showed higher patency rates (p < 0.01).

Conclusion

After comprehensive DUS evaluation, intraoperative hydrodilation, postoperative active exercise and intensive DUS detection, and application of balloon-assisted maturation, if necessary, using a vein more than 1.35 mm (augmented), could achieve satisfactory functional maturation and postoperative patency in AVF formation.
The major factor of left ventricular systolic dysfunction in patients with cardiac amyloidosis: Amyloid overload or microcirculation impairment?
Authors: Lu Jianyao , Zhao Peijun , Qiao Jinhan , Yang Zhaoxia , Tang Dazhong , Zhou Xiaoyue , Huang Lu , Xia Liming
Published: January 2023

Purpose

Amyloid overload and microcirculation impairment are both detrimental to left ventricular (LV) systolic function, while it is not clear which factor dominates LV functional remodeling in patients with cardiac amyloidosis (CA). The purpose of this study was to investigate the major factor of LV systolic dysfunction using cardiac magnetic resonance imaging.

Materials and methods

Forty CA patients and 20 healthy controls were included in this study. The CA group was divided into two subgroups by the left ventricular ejection fraction (LVEF): patients with reduced LVEF (LVEF < 50%, rLVEF), and patients with preserved LVEF (LVEF ≥ 50%, pLVEF). The scanning sequences included cine, native and post-contrast T1 mapping, rest first-pass perfusion and late gadolinium enhancement. Perfusion and mapping parameters were compared among the three groups. Correlation analysis was performed to evaluate the relationship between LVEF and mapping parameters, as well as the relationship between LVEF and perfusion parameters.

Results

Remarkably higher native T1 value was observed in the rLVEF patients than the pLVEF patients (1442.2 ± 85.8 ms vs. 1407.0 ± 93.9 ms, adjusted p = 0.001). The pLVEF patients showed significantly lower slope dividing baseline signal intensity (slope%BL; rLVEF vs. pLVEF, 55.1 ± 31.0 vs. 46.2 ± 22.3, adjusted p = 0.001) and a lower maximal signal intensity subtracting baseline signal intensity (MaxSI-BL; rLVEF vs. pLVEF, 43.5 ± 23.9 vs. 37.0 ± 18.6, adjusted p = 0.003) compared to the rLVEF patients. CA patients required more time to reach the maximal signal intensity than the controls did (all adjusted p < 0.01). There was no significant correlation between LVEF and first-pass perfusion parameters, while significant negative correlation was observed between LVEF and native T1 (r = −0.434, p = 0.005) in CA patients.

Conclusion

Amyloid overload in the myocardial interstitium may be the major factor of LV systolic dysfunction in CA patients, other than microcirculation impairment.
Pharmacologic inhibition by spironolactone attenuates experimental abdominal aortic aneurysms
Authors: Ladd Zachary , Su Gang , Hartman Joseph , Lu Guanyi , Hensley Sara , Upchurch Gilbert R. , Sharma Ashish K.
Published: January 2023

Background

Abdominal aortic aneurysms (AAA) are characterized by vascular inflammation and remodeling that can lead to aortic rupture resulting in significant mortality. Pannexin-1 channels on endothelial cells (ECs) can modulate ATP secretion to regulate the pathogenesis of AAA formation. Our hypothesis focused on potential of spironolactone to inhibit EC-mediated ATP release for the mitigation of AAA formation.

Methods

A topical elastase AAA model was used initially in C57BL/6 (wild-type; WT) male mice. Mice were administered either a vehicle control (saline) or spironolactone and analyzed on day 14. In a second chronic AAA model, mice were subjected to elastase and β-aminopropionitrile (BAPN) treatment with/without administration of spironolactone to pre-formed aneurysms starting on day 14 and analyzed on day 28. Aortic diameter was evaluated by video micrometry and aortic tissue was analyzed for cytokine expression and histology. ATP measurement and matrix metalloproteinase (MMP2) activity was evaluated in aortic tissue on days 14 or -28. In vitro studies were performed to evaluate the crosstalk between aortic ECs with macrophages or smooth muscle cells.

Results

In the elastase AAA model, spironolactone treatment displayed a significant decrease in aortic diameter compared to elastase-treated controls on day 14. A significant increase in smooth muscle α-actin expression as well as decrease in elastic fiber disruption and immune cell (macrophages and neutrophils) infiltration was observed in mice treated with spironolactone compared to saline-treated controls. Spironolactone treatment also significantly mitigated pro-inflammatory cytokine expression, MMP2 activity and ATP content in aortic tissue compared to controls. Moreover, in the chronic AAA model, spironolactone treatment of pre-formed aneurysms significantly attenuated vascular inflammation and remodeling to attenuate the progression of AAAs compared to controls. Mechanistically, in vitro data demonstrated that spironolactone treatment attenuates extracellular ATP release from endothelial cells to mitigate macrophage activation (IL-1β and HMGB1 expression) and smooth muscle cell-dependent vascular remodeling (MMP2 activity).

Conclusion

These results demonstrate that spironolactone can mitigate aortic inflammation and remodeling to attenuate AAA formation as well as decrease growth of pre-formed aneurysms via inhibition of EC-dependent ATP release. Therefore, this study implicates a therapeutic application of spironolactone in the treatment of AAAs.
Research on key parameters of pipeline transportation of waste rock treatment in underground residual space
Authors: Gu Wenzhe , Zhu Lei , Song Tianqi
Published: January 2023

As the key link of coal gangue slurry filling, slurry pipeline transportation is an important guarantee to realize the slurry mixing and safe transportation of gangue from solid powder. To realize the underground excavation gangue of the Huangling No. 2 coal mine without raising the ground, the slurry filling technology is proposed to transport the slurry made by gangue through the pipeline and fill it into the goaf. The phase composition and microstructure characteristics of underground excavation gangue in the Huangling No. 2 coal mine were analyzed by X-ray diffraction and an electron microscope scanning test, the slurry-forming properties of gangue powder with different particle sizes and gradations were studied, and the influence of gangue slurry concentration on its rheological properties was analyzed. The experimental results show that the gangue powder crushed using a cage crusher can be made into stable slurry when the particle grading size is the natural crushing gradation with the upper limit of particle size less than 3 mm. The viscosity of the slurry is positively correlated with the concentration. When the concentration is below 70%, the increase in viscosity is small, and when the concentration is above 70%, the increase in viscosity is significant. It is determined that the concentration of the Huangling No. 2 coal mine slurry is 70%. Based on the determination of slurry preparation parameters, the simulation analysis of slurry pipeline transportation was carried out, the influence of design velocity on the velocity distribution of the pipeline section and the variation law of slurry concentration was explored, and the design velocity of the project is determined to be 1.5 m/s. The engineering practice shows that the slurry preparation parameters are reasonable. The crushing and pulping of gangue under the ground and the safe transportation of a 6 km pipeline are realized, which provides a reference for similar engineering projects.
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 objective

Glycation 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.

Methods

In 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.

Results

With 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 > 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 < 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 > 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 < 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 < 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 < 0.05).

Conclusion

The 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

Objectives

Studies 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.

Methods

Retrospective 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.

Results

Glucose levels significantly differed during the day (i.e., morning to evening; P<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<0.001 and SD; 0.49 mmol/L vs 0.38 mmol/L, P<0.001). When comparing treatment methods, mean glucose (6.09 vs 5.65 mmol/L; P<0.001) and AUC (8760.8 vs 8115.1 mmol/L.hr; P<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).

Conclusions

Glycemia 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.
Effects of neutral polysaccharide from Platycodon grandiflorum on high-fat diet-induced obesity via the regulation of gut microbiota and metabolites
Authors: Song Jing , liu Qin , Hao Mengqi , Zhai Xiaohu , Chen Juan
Published: January 2023

The obesity epidemic has become a global problem with far-reaching health and economic impact. Despite the numerous therapeutic efficacies of Platycodon grandiflorum, its role in modulating obesity-related metabolic disorders has not been clarified. In this study, a purified neutral polysaccharide, PGNP, was obtained from Platycodon grandiflorum. Based on methylation and NMR analyses, PGNP was found to be composed of 2,1-β-D-Fruf residues ending with a (1→2)-bonded α-D-Glcp. The protective effects of PGNP on high-fat HFD-induced obesity were assessed. According to our results, PGNP effectively alleviated the signs of metabolic syndrome, as demonstrated by reductions in body weight, hepatic steatosis, lipid profile, inflammatory response, and insulin resistance in obese mice. Under PGNP treatment, intestinal histomorphology and the tight junction protein, ZO-1, were well maintained. To elucidate the underlying mechanism, 16S rRNA gene sequencing and LC-MS were employed to assess the positive influence of PGNP on the gut microbiota and metabolites. PGNP effectively increased species diversity of gut microbiota and reversed the HFD-induced imbalance in the gut microbiota by decreasing the Firmicutes to Bacteroidetes ratio. The abundance of Bacteroides and Blautia were increased after PGNP treatment, while the relative abundance of Rikenella, Helicobacter were reduced. Furthermore, PGNP notably influenced the levels of microbial metabolites, including the increased levels of cholic and gamma-linolenic acid. Overall, PGNP might be a potential supplement for the regulation of gut microbiota and metabolites, further affecting obesity.
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

Background

The 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.

Methods

A 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.

Results

The 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 < 0.05), or of poor reproductive potential with a cutoff value of 2.515 (AUC = 66.3%, P < 0.05). The SD6 FSH/LH ratio predicted poor reproductive potential with a cutoff value of 4.14 (AUC = 63.8%, P < 0.05). The trigger day FSH/LH ratio predicted poor responders with a cutoff value of 9.665 (AUC = 63.1%, P < 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.

Conclusions

FSH/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

Aim

To identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM).

Methods

T2DM 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.

Results

A 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 <0.05). In the final regression model, AGI use (adjusted OR=4.01, 95%CI: 1.90-8.45, p<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<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.

Conclusion

This 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

Background

Klinefelter 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.

Methods

Adolescents 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.

Results

Nineteen 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.

Conclusion

A 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.
Evolution of sodium-glucose co-transporter 2 inhibitors from a glucose-lowering drug to a pivotal therapeutic agent for cardio-renal-metabolic syndrome
Authors: Akiyama Hiroki , Nishimura Akihiro , Morita Naru , Yajima Toshitaka
Published: January 2023

Cardio-renal-metabolic (CRM) syndrome, which involves type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and heart failure (HF), is a serious healthcare issue globally, with high morbidity and mortality. The disorders that comprise CRM syndrome are independent can mutually affect and accelerate the exacerbation of each other, thereby substantially increasing the risk of mortality and impairing quality of life. To manage CRM syndrome by preventing vicious interactions among individual disorders, a holistic treatment approach that can simultaneously address multiple disorders underpinning CRM syndrome is of great importance. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) lower blood glucose levels by inhibiting glucose reabsorption in the renal proximal tubule and were first indicated for the treatment of T2DM. Several cardiovascular outcome trials have demonstrated that SGLT2i not only lower blood glucose but also reduce the risk of hospitalization for HF and worsening renal function in patients with T2DM. Results have also suggested that the observed cardiorenal benefits of SGLT2i may be independent of their blood glucose-lowering effects. Several randomized controlled trials subsequently assessed the efficacy and safety of SGLT2i in patients without T2DM, and revealed considerable benefits of SGLT2i treatment against HF and CKD, regardless of the presence of T2DM. Thus, SGLT2i have become an essential therapeutic option to prevent the onset, slow the progression, and improve the prognosis of CRM syndrome. This review assesses the evolution of SGLT2i from a glucose-lowering drug to a therapeutic agent for CRM syndrome by evaluating epoch-making clinical studies, including randomized control trials and real-world studies.
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

Background

Environmental 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.

Methods

A 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)

Results

Out 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.

Conclusion

In 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 registration

https://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

Background

Gastric 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.

Methods

In 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.

Results

A 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.

Conclusion

The 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.
Development and verification of lead-bismuth cooled fast reactor calculation code system Mosasaur
Authors: Zhang Bin , Wang Lianjie , Lou Lei , Zhao Chen , Peng Xingjie , Yan Mingyu , Xia Bangyang , Zhang Ce , Qiao Liang , Wu Qu
Published: January 2023

Lead-bismuth cooled fast reactor calculation code system named MOSASAUR has been developed to meet the simulation requirements from LBFR engineering design. An overview of MOSASAUR developments is provided in this paper, four main functional modules and their models are introduced: cross-sections generation module, flux spectrum correction module, core simulation module and sensitivity and uncertainty analysis module. Verification and validation results of numerical benchmark calculations, code-to-code comparisons with the Monte-Carlo code and critical experimental calculations shown in this paper prove the capabilities of MOSASAUR in dealing with lead-bismuth cooled fast reactor analysis problems with good performances. Numerical results demonstrate that compared with the Monte-Carlo code, the relative errors of eigenvalues are smaller than 350pcm when the calculations were carried out with the same nuclear data file. Compared with the measured values, the errors will increase due to the simulation details and the measurement accuracy.
Genome-wide association study finds multiple loci associated with intraocular pressure in HS rats
Authors: Fowler Samuel , Wang Tengfei , Munro Daniel , Kumar Aman , Chitre Apurva S. , Hollingsworth T. J. , Garcia Martinez Angel , St. Pierre Celine L. , Bimschleger Hannah , Gao Jianjun , Cheng Riyan , Mohammadi Pejman , Chen Hao , Palmer Abraham A. , Polesskaya Oksana , Jablonski Monica M.
Published: January 2023

Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. Increased IOP is a major risk factor for most types of glaucoma, including primary open angle glaucoma (POAG). Investigating the genetic basis of IOP may lead to a better understanding of the molecular mechanisms of POAG. The goal of this study was to identify genetic loci involved in regulating IOP using outbred heterogeneous stock (HS) rats. HS rats are a multigenerational outbred population derived from eight inbred strains that have been fully sequenced. This population is ideal for a genome-wide association study (GWAS) owing to the accumulated recombinations among well-defined haplotypes, the relatively high allele frequencies, the accessibility to a large collection of tissue samples, and the large allelic effect size compared to human studies. Both male and female HS rats (N = 1,812) were used in the study. Genotyping-by-sequencing was used to obtain ∼3.5 million single nucleotide polymorphisms (SNP) from each individual. SNP heritability for IOP in HS rats was 0.32, which agrees with other studies. We performed a GWAS for the IOP phenotype using a linear mixed model and used permutation to determine a genome-wide significance threshold. We identified three genome-wide significant loci for IOP on chromosomes 1, 5, and 16. Next, we sequenced the mRNA of 51 whole eye samples to find cis-eQTLs to aid in identification of candidate genes. We report 5 candidate genes within those loci: Tyr, Ctsc, Plekhf2, Ndufaf6 and Angpt2. Tyr, Ndufaf6 and Angpt2 genes have been previously implicated by human GWAS of IOP-related conditions. Ctsc and Plekhf2 genes represent novel findings that may provide new insight into the molecular basis of IOP. This study highlights the efficacy of HS rats for investigating the genetics of elevated IOP and identifying potential candidate genes for future functional testing.
Molecular evolution and population genetics of glutamate decarboxylase acid resistance pathway in lactic acid bacteria
Authors: Sezgin Efe , Tekin Burcu
Published: January 2023

Glutamate decarboxylase (GAD) pathway (GDP) is a major acid resistance mechanism enabling microorganisms’ survival in low pH environments. We aimed to study the molecular evolution and population genetics of GDP in Lactic Acid Bacteria (LAB) to understand evolutionary processes shaping adaptation to acidic environments comparing species where the GDP genes are organized in an operon structure (Levilactobacillus brevis) versus lack of an operon structure (Lactiplantibacillus plantarum). Within species molecular population genetic analyses of GDP genes in L. brevis and L. plantarum sampled from diverse fermented food and other environments showed abundant synonymous and non-synonymous nucleotide diversity, mostly driven by low frequency changes, distributed throughout the coding regions for all genes in both species. GAD genes showed higher level of replacement polymorphism compared to transporter genes (gadC and YjeM) for both species, and GAD genes that are outside of an operon structure showed even higher level of replacement polymorphism. Population genetic tests suggest negative selection against replacement changes in all genes. Molecular structure and amino acid characteristics analyses showed that in none of the GDP genes replacement changes alter 3D structure or charge distribution supporting negative selection against non-conservative amino acid changes. Phylogenetic and between species divergence analyses suggested adaptive protein evolution on GDP genes comparing phylogenetically distant species, but conservative evolution comparing closely related species. GDP genes within an operon structure showed slower molecular evolution and higher conservation. All GAD and transporter genes showed high codon usage bias in examined LAB species suggesting high expression and utilization of acid resistance genes. Substantial discordances between species, GAD, and transporter gene tree topologies were observed suggesting molecular evolution of GDP genes do not follow speciation events. Distribution of operon structure on the species tree suggested multiple independent gain or loss of operon structure in LABs. In conclusion, GDP genes in LABs exhibit a dynamic molecular evolutionary history shaped by gene loss, gene transfer, negative and positive selection to maintain its active role in acid resistance mechanism, and enable organisms to thrive in acidic environments.
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.
DSS-induced colitis activates the kynurenine pathway in serum and brain by affecting IDO-1 and gut microbiota
Authors: Zhao Li-Ping , Wu Jian , Quan Wei , Zhou Yu , Hong Hui , Niu Gu-Yu , Li Ting , Huang Shu-Bing , Qiao Chen-Meng , Zhao Wei-Jiang , Cui Chun , Shen Yan-Qin
Published: January 2023

Accumulative studies suggest that inflammatory bowel disease (IBD) may cause multiple central nervous system (CNS) pathologies. Studies have found that indoleamine-2,3-dioxygenase (IDO, rate-limiting enzyme of the kynurenine (Kyn) pathway) deficient mice were protected from endotoxin induced cognitive impairment, and Kyn administration induced cognitive memory deficits in both control and IDO-deficient mice. However, there is no investigation of the brain Kyn pathway in IBD, thus we investigated whether dextran sulfate sodium (DSS)-induced colitis could cause dysregulation of Kyn pathway in brain, and also in serum. C57BL/6J mice were given drinking water with 2% DSS for 10 consecutive days to induce colitis. In serum, we found significant increase in Kyn and kynurenic acid (Kyna) level, which was regulated by IDO-1 and KAT2 (rate-limiting enzymes of Trp-Kyn-Kyna pathway). Similarly, by analyzing GEO datasets, higher IDO-1 levels in peripheral blood monocytes and colon of UC patients was found. Furthermore, the Kyn pathway was significantly upregulated in the cerebral cortex under the action of IDO-1 after DSS treatment, which ultimately induced the neurotoxic phenotype of astrocytes. To investigate whether gut microbiota is involved in IBD-induced Kyn pathway dysregulation, we performed intestinal flora 16S rRNA sequencing and found that DSS-induced colitis significantly altered the composition and diversity of the gut microbiota. Metabolic function analysis also showed that Tryptophan metabolism, NOD-like receptor signaling pathway and MAPK signaling pathway were significantly up-regulated in the 2% DSS group. A significant association between intestinal flora and Trp metabolism (both in serum and brain) was found by correlation analysis. Overall, this study revealed that DSS-induced colitis causes dysregulation of the Kyn pathway in serum and brain by affecting rate-limiting enzymes and intestinal flora.
Chemical biology tools to interrogate the roles of O-GlcNAc in immunity
Authors: Saha Abhijit , Fernández-Tejada Alberto
Published: January 2023

The O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of proteins is an essential and dynamic post-translational modification in mammalian cells that is regulated by the action of two enzymes. O-GlcNAc transferase (OGT) incorporates this monosaccharide on serine/threonine residues, whereas O-GlcNAcase (OGA) removes it. This modification is found on thousands of intracellular proteins involved in vital cellular processes, both under physiological and pathological conditions. Aberrant expression of O-GlcNAc has been implicated in diseases such as Alzheimer, diabetes, and cancer, and growing evidence over the last decade has also revealed key implications of O-GlcNAcylation in immunity. While some key signaling pathways involving O-GlcNAcylation in immune cells have been discovered, a complete mechanistic understanding of how O-GlcNAcylated proteins function in the immune system remains elusive, partly because of the difficulties in mapping and quantifying O-GlcNAc sites. In this minireview, we discuss recent progress on chemical biology tools and approaches to investigate the role of O-GlcNAcylation in immune cells, with the intention of encouraging further research and developments in chemical glycoimmunology that can advance our understanding of O-GlcNAc in immunity.
The role of pyroptosis in endothelial dysfunction induced by diseases
Authors: Ju Jin , Liu Yanyan , Liang Haihai , Yang Baofeng
Published: January 2023

Most organs in the body rely on blood flow, and vesicular damage is the leading cause of injury in multiple organs. The endothelium, as the barriers of vessels, play a critical role in ensuring vascular homeostasis and angiogenesis. The rapid development of risk factors in endothelial injuries has been seen in the past decade, such as smoking, infectious, and diabetes mellites. Pyroptotic endothelium is an inflammatory mode of governed endothelial cell death that depend on the metabolic disorder and severe infectious such as atherosclerosis, and sepsis-related acute lung injury, respectively. Pyroptotic endothelial cells need GSDMD cleaved into N- and C-terminal by caspase1, and the cytokines are released by a pore constructed by the N-terminal of GSDMD in the membrane of ECs, finally resulting in severe inflammation and pyroptotic cell death. This review will focus on the patho-physiological and pharmacological pathways of pyroptotic endothelial metabolism in diseases. Overall, this review indicates that pyroptosis is a significant risk factor in diseases and a potential drug target in related diseases.
Generation of mesenchymal stromal cells from urine-derived iPSCs of pediatric brain tumor patients
Authors: Baliña-Sánchez Carmen , Aguilera Yolanda , Adán Norma , Sierra-Párraga Jesús María , Olmedo-Moreno Laura , Panadero-Morón Concepción , Cabello-Laureano Rosa , Márquez-Vega Catalina , Martín-Montalvo Alejandro , Capilla-González Vivian
Published: January 2023

Human induced pluripotent stem cells (iPSCs) provide a virtually inexhaustible source of starting material for next generation cell therapies, offering new opportunities for regenerative medicine. Among different cell sources for the generation of iPSCs, urine cells are clinically relevant since these cells can be repeatedly obtained by non-invasive methods from patients of any age and health condition. These attributes encourage patients to participate in preclinical and clinical research. In particular, the use of urine-derived iPSC products is a convenient strategy for children with brain tumors, which are medically fragile patients. Here, we investigate the feasibility of using urine samples as a source of somatic cells to generate iPSC lines from pediatric patients with brain tumors (BT-iPSC). Urinary epithelial cells were isolated and reprogrammed using non-integrative Sendai virus vectors harboring the Yamanaka factors KLF4, OCT3/4, SOX2 and C-MYC. After reprogramming, BT-iPSC lines were subject to quality assessment and were compared to iPSCs obtained from urine samples of non-tumor pediatric patients (nonT-iPSC). We demonstrated that iPSCs can be successfully derived from a small volume of urine obtained from pediatric patients. Importantly, we showed that BT-iPSCs are equivalent to nonT-iPSCs in terms of morphology, pluripotency, and differentiation capacity into the three germ layers. In addition, both BT-iPSCs and nonT-iPSCs efficiently differentiated into functional mesenchymal stem/stromal cells (iMSC) with immunomodulatory properties. Therefore, this study provides an attractive approach to non-invasively generate personalized iMSC products intended for the treatment of children with brain tumors.