bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bibliometric and visualized analysis of sodium–Glucose cotransporter 2 inhibitors
Authors: Sun He , Wang Zhongqing , Wang Yuxi , Rong Haichuan , Wang Danyang , Liu Xiangnian , Jin Ke , Sun Zhicheng , Fan Qiuling 
Published: January 2023

Background: Sodium—glucose cotransporter 2 inhibitors have proved to be extremely effective and reliable in reducing hyperglycemia, and have also been used for the treatment of cardiovascular and renal disease in patients with or without type 2 diabetes. Thousands of research articles on SGLT2 inhibitors have been published in the past, but few bibliometric analyses have systematically been studied this field. We aimed to visualize the global research hotspots and trends of SGLT2 inhibitors using a bibliometric analysis to provide new evidence and ideas for researchers and clinicians in this field.Methods: We retrieved publications from Science Citation Index Expanded of Web of Science Core Collection in 2004–2022 on 1 July 2022. Microsoft Excel, CiteSpace and VOSviewer were employed to collect publication data, analyze publication trends, and visualize relevant results.Results: We identified 4,419 original research articles on SGLT2 inhibitors published between 2004 and the first half of 2022. Global SGLT2 inhibitors-related research increased rapidly from 2004 to 2022, especially recently. United States made the greatest contribution to the topic, with (1,629, 36.86%) publications and citations (88,892). AstraZeneca was the most prolific institutions (272, 6.16%). Heerspink HJL published the most related articles (98), whereas Zinman B was cited the most frequently (1,784 citations). Diabetes Obesity and Metabolism was the journal with the most studies (406, 9.19%), and The New England Journal of Medicine was the most commonly cited journal (11,617 citations), with nine of the top 10 co-cited references published in this journal. The emerging keywords “heart failure,” “diabetic cardiomyopathy,” “ejection fraction,” “mortality,” “biomarker,” “fibrosis,” “ampk,” and “guideline” appeared the most recently as research frontiers.Conclusion: United States is the leader in SGLT2 inhibitor research. Recently, the research on SGLT2 inhibitors has focused on clinical trials, related mechanisms, and therapy. In the future, the research on SGLT2 inhibitors will delve into molecular mechanisms, especially those related to fibrosis and AMPK, revealing the link between SGLT2 inhibitors and heart failure and diabetic cardiomyopathy will be the next research hotspot.
Comparative differences in the risk of major gastrointestinal bleeding among different direct oral anticoagulants: An updated traditional and Bayesian network meta-analysis
Authors: Chen Xiuehui , Wang Lili , Li Huijun , Huang Weichao , Zhao Lingyue , Guo Wenqin 
Published: January 2023

Background: The most favorable gastrointestinal (GI) bleeding safety profile among different types of direct oral anticoagulants (DOACs) remains controversial. This meta-analysis includes the latest studies and aims to compare GI bleeding risk associated with the use of various DOACs.Methods: PubMed, Cochrane library, and clinicaltrial.gov were searched. Randomized control trials (RCTs) evaluating the safety of DOACs were identified. The primary endpoint assessed was major GI bleeding.Results: A total of 37 RCTs were included in the analyses. Based on the traditional meta-analysis, the major GI bleeding risk was different among various DOACs (interactive p-value &lt;.10). Network meta-analysis findings showed that no DOACs increased the risk of major GI bleeding compared with conventional therapy. Furthermore, a 10 mg daily administration of apixaban reduced the major GI bleeding risk more than daily doses of 60 mg edoxaban, ≥15 mg rivaroxaban, and 300 mg dabigatran etexilate. No difference was observed between daily doses of 300 mg dabigatran etexilate, 60 mg edoxaban, and ≥15 mg rivaroxaban. The major GI bleeding risk associated with 30 mg daily dose of edoxaban was lower than with 10 mg daily rivaroxaban, and no differences between daily 5 mg apixaban, 30 mg edoxaban, and 220 mg dabigatran etexilate were observed.Conclusion: Differences in the major GI bleeding risk were observed when various DOACs were compared. Among standard-dose DOACs, apixaban was associated with the lowest degree of major GI risk. Among low-dose DOACs, edoxaban was associated with a lower major GI bleeding risk than rivaroxaban.
Necroptotic kinases are involved in the reduction of depression-induced astrocytes and fluoxetine’s inhibitory effects on necroptotic kinases
Authors: Zeb Salman , Ye Huan , Liu Yuan , Du Hua-Ping , Guo Yi , Zhu Yong-Ming , Ni Yong , Zhang Hui-Ling , Xu Yuan 
Published: January 2023

The role of astrocytes in major depressive disorder has received great attention. Increasing evidence indicates that decreased astrocyte numbers in the hippocampus may be associated with depression, but the role of necroptosis in depression is unknown. Here, in a chronic unpredictable mild stress (CUMS) mouse model and a corticosterone (Cort)-induced human astrocyte injury model in vitro, we found that mice treated with chronic unpredictable mild stress for 3–5 weeks presented depressive-like behaviors and reduced body weight gain, accompanied by a reduction in astrocytes and a decrease in astrocytic brain-derived neurotropic factors (BDNF), by activation of necroptotic kinases, including RIPK1 (receptor-interacting protein kinase 1)/p-RIPK1, RIPK3 (receptor-interacting protein kinase 3)/p-RIPK3 and MLKL (mixed lineage kinase domain-like protein)/p-MLKL, and by upregulation of inflammatory cytokines in astrocytes of the mouse hippocampus. In contrast, necroptotic kinase inhibitors suppressed Cort-induced necroptotic kinase activation, reduced astrocytes, astrocytic necroptosis and dysfunction, and decreased Cort-mediated inflammatory cytokines in astrocytes. Treatment with fluoxetine (FLX) for 5 weeks improved chronic unpredictable mild stress-induced mouse depressive-like behaviors; simultaneously, fluoxetine inhibited depression-induced necroptotic kinase activation, reversed the reduction in astrocytes and astrocytic necroptosis and dysfunction, decreased inflammatory cytokines and upregulated brain-derived neurotropic factors and 5-HT1A levels. Furthermore, fluoxetine had no direct inhibitory effect on receptor-interacting protein kinase 1 phosphorylation. The combined administration of fluoxetine and necroptotic kinase inhibitors further reduced corticosterone-induced astrocyte injury. In conclusion, the reduction in astrocytes caused by depressive-like models in vivo and in vitro may be associated with the activation of necroptotic kinases and astrocytic necroptosis, and fluoxetine exerts an antidepressive effect by indirectly inhibiting receptor-interacting protein kinase 1-mediated astrocytic necroptosis.
Combination therapy of cisplatin and resveratrol to induce cellular aging in gastric cancer cells: Focusing on oxidative stress, and cell cycle arrest
Authors: Rahimifard Mahban , Baeeri Maryam , Mousavi Taraneh , Azarnezhad Asaad , Haghi-Aminjan Hamed , Abdollahi Mohammad 
Published: January 2023

Background: As a medical dilemma, gastric cancer will have 7.3 million new cases in 2040. Despite the disease’s high economic and global burden, conventional chemotherapy regimens containing cisplatin have insufficient effectiveness and act non-specifically, leading to several adverse drug reactions To address these issues, the biological efficacy of the cisplatin-resveratrol combination was tested.Methods: To find IC50, gastric adenocarcinoma cells (AGS) were exposed to different concentrations of resveratrol and cisplatin. Anti-cancer and anti-metastatic effects of 100 M resveratrol with concentrations of cisplatin (25, 50, and 100 g/ml) were studied by assessing ß-galactosidase and telomerase activities, senescence and migration gene expression, reactive oxygen species (ROS) level, and cell cycle arrest.Results: Co-administration of cisplatin and resveratrol increased ß-galactosidase activity, ROS level as a key marker of oxidative stress, p53, p38, p16, p21, and MMP-2 gene expression, and induced G0/G1 cell cycle arrest. Additionally, telomerase activity, pro-inflammatory gene expression, and cell invasion were suppressed. The best results were achieved with 100 g/ml cisplatin co-administered with resveratrol.Conclusion: The current study proved the synergistic effect of the cisplatin-resveratrol combination on suppressing metastasis and inducing apoptosis and cell senescence through targeting P38/P53 and P16/P21 pathways. Such promising results warrant translation to animal models and the clinic. This may lead to cost-effective, available, and accessible treatment regimens with targeted action and the fewest ADRs.
Amelioration of cognitive impairment using epigallocatechin-3-gallate in ovariectomized mice fed a high-fat diet involves remodeling with Prevotella and Bifidobacteriales
Authors: Qu Yang , Wu Yan , Cheng Wei , Wang Dongyang , Zeng Lu , Wang Yanru , Li Tingting , Zhang Liye , Yang Jinan , Sun Liyang , Ai Jing 
Published: January 2023

Background: Estrogen deficiency and a high-fat diet (HFD) are both risk factors for Alzheimer’s disease (AD). HFD can accelerate cognitive impairment in estrogen-deficient patients, but there is currently no effective treatment. Epigallocatechin-3-galate (EGCG) is widely studied for its anti-inflammatory, anti-cancer, and anti-neurodegeneration effects. Nevertheless, whether EGCG can ameliorate cognitive impairment in HFD-fed estrogen-deficient mice has not been studied.Methods and Results: Ovariectomized (OVX) mice fed an HFD (HFOVX) for 8 weeks experienced impaired object recognition and spatial memory, but this damage was significantly attenuated by the administration of EGCG at a dose of 45 mg/kg. Through 16S rRNA gene sequencing, we found that HFOVX changed the diversity and structure of the gut microbiota in mice, which could be restored with EGCG. Further analysis showed that HFOVX exposure not only resulted in a decrease of Alloprevotella in Bacteroidetes, Lactobacillaceae in Firmicutes, and Prevotella in Bacteroidetes but also in an increase of Bifidobacteriales in Actinobacteria. EGCG effectively reversed the decrease of Prevotella and inhibited the increase of Bifidobacteriales but had no effect on the decrease of Alloprevotella or Lactobacillaceae or on the increase of Enterorhabdus in HFOVX mice. Additionally, using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we found that EGCG significantly reversed the five functional gut microbiota genes elevated by HFOVX, including iron complex transport system substrate-binding protein, iron complex transport system permease protein, 3-oxoacyl- [acyl-carrier protein] reductase, transketolase, and 8-oxo-dGTP diphosphatase.Conclusions: We concluded that EGCG improved cognitive impairment in mice with estrogen deficiency exacerbated by an HFD involved a rebuilding of the disrupted gut microbiota composition.
The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo
Authors: Cui Lili , Peng Chaorui , Li Jun , Cheng Xin , Fan Xiao , Li Jingyu , Yang Zixian , Zhao Yuancui , Ma Yunshu 
Published: January 2023

Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy.Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved.Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels.Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1β and TNF-α) by LPS-induced RAW264.7 macrophages (p &lt; .01).Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.
Therapeutic effect and rebound evaluation of dapagliflozin on glycated hemoglobin (HbA1c) in type 1 diabetes mellitus patients
Authors: Wang Dong-Dong , Zhang Cun , Hu Ke , He Su-Mei , Zhu Ping , Chen Xiao 
Published: January 2023

Dapagliflozin has been used to treat patients with type 1 diabetes mellitus; however, the actual drug efficacy of dapagliflozin on glycated hemoglobin (HbA1c) and whether there is a rebound from dapagliflozin efficacy on HbA1c remain unknown. The present study aimed to explore the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients. A total of 1,594 type 1 diabetes mellitus patients were enrolled for analysis using a non-linear mixed effect model from randomized controlled trials from published literature works including two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups. The change rate of HbA1c from a baseline value was chosen as a dapagliflozin pharmacodynamic evaluation index. After deducting control group effects, the therapeutic effect of 5 and 10 mg/day dapagliflozin on HbA1c in type 1 diabetes mellitus patients had no significant difference. In addition, the actual maximal efficacy (AEmax) of dapagliflozin on HbA1c was -6.24% at week 9. When it reached the AEmax, the dapagliflozin pharmacodynamic rebound on HbA1c occurred, and when the treatment was continued for 0.5 and 1 year, the actual efficacies were -4.70% (75% AEmax) and -3.27% (52% AEmax), respectively. This was the first time to clarify the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients, providing a reference value for clinical practices.
Evaluation of Mollugo oppositifolia Linn. as cholinesterase and β-secretase enzymes inhibitor
Authors: Das Bhaskar , Bhardwaj Pardeep K. , Sharma Nanaocha , Sarkar Arnab , Haldar Pallab Kanti , Mukherjee Pulok K. 
Published: January 2023

Mollugo oppositifolia Linn. is traditionally used in neurological complications. The study aimed to investigate in-vitro neuroprotective effect of the plant extracts through testing against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase linked to Alzheimer’s disease (AD). To understand the safety aspects, the extracts were tested for CYP450 isozymes and human hepatocellular carcinoma cell (HepG2) inhibitory potential. The heavy metal contents were estimated using atomic absorption spectroscopy (AAS). Further, the antioxidant capacities as well as total phenolic content and total flavonoid content (TFC) were measured spectrophotometrically. UPLC-QTOF-MS/MS analysis was employed to identify phytometabolites present in the extract. The interactions of the ligands with the target proteins (AChE, BChE, and BACE-1) were studied using AutoDockTools 1.5.6. The results showed that M. oppositifolia extract has more selectivity towards BChE (IC50 = 278.23 ± 1.89 μg/ml) as compared to AChE (IC50 = 322.87 ± 2.05 μg/ml). The IC50 value against β-secretase was 173.93 μg/ml. The extract showed a CC50 value of 965.45 ± 3.07 μg/ml against HepG2 cells and the AAS analysis showed traces of lead 0.02 ± 0.001 which was found to be within the WHO prescribed limits. Moreover, the IC50 values against CYP3A4 (477.03 ± 2.01 μg/ml) and CYP2D6 (249.65 ± 2.46 μg/ml) isozymes justify the safety aspects of the extract. The in silico molecular docking analysis of the target enzymes showed that the compound menthoside was found to be the most stable and showed a good docking score among all the identified metabolites. Keeping in mind the multi-targeted drug approach, the present findings suggested that M. oppositifolia extract have anti-Alzheimer’s potential.
A robust self-referenced 2D nyquist ghost correction for different MRI-biomarker measurements based on multi-band interleaved EPI
Authors: Liu Xiaoxi , Chen Shihui , Cui Di , Hui Edward S. , Chan Queenie , Chen Nan-Kuei , Chang Hing-Chiu 
Published: January 2023

Purpose: To enable 2D Nyquist ghost correction for multi-band interleaved echo-planar imaging (EPI) without reference scan.Methods: 2D phase errors between positive and negative echo were directly measured from the multi-band interleaved EPI data acquired with alternating readout polarity, and then corrected by using multiplexed sensitivity encoding (MUSE) framework. The proposed method was tested on brain data acquired with and without multi-band imaging under different multi-shot factors (4, 8, and 16). In addition, the 2D phase corrections for the interleaved EPI data acquired with 2D zoomed-FOV, 2D reduced-FOV, or 3D multi-band imaging were also performed with the proposed method. The performance of our proposed method was assessed with single-to-noise ratio (SNR) and ghost-to-signal ratio (GSR), and then compared with an iterative 2D phase correction method. The g-factor penalty of the proposed 2D Nyquist ghost correction method associated with 2D phase error was also evaluated. The feasibility of the proposed method was evaluated in diffusion MRI and multi-echo fMRI where quantitative biomarkers with high quality are desired.Results: The proposed method successfully suppressed the ghost artifacts for the multi-shot interleaved EPI data acquired with different multi-shot factors, 2D and 3D multi-band acquisitions, zoomed-FOV, or reduced-FOV. Compared with the iterative method, our proposed method showed lower GSR and comparable SNR performance. Through g-factor penalty simulation, the proposed method showed less than 9% of overall SNR loss associated with a maximum y-linear phase error of π. The residual aliasing artifact was effectively eliminated in the quantitative biomarkers (ADC, FA and dynamic T2*) when applying the proposed method in diffusion imaging and multi-echo fMRI.Conclusion: The proposed method can perform robust 2D Nyquist ghost correction for multi-band multi-shot interleaved EPI without reference scan, and thus can be a generalized 2D ghost correction method for multi-shot interleaved EPI based acquisitions and applications.
Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
Authors: Kurgan Nigel , Baranowski Bradley , Stoikos Joshua , MacNeil Adam J. , Fajardo Val A. , MacPherson Rebecca E. K. , Klentrou Panagiota 
Published: January 2023

Introduction: It is well established that sclerostin antagonizes the anabolic Wnt signalling pathway in bone, however, its physiological role in other tissues remains less clear. This study examined the effect of a high-fat diet (HFD) on sclerostin content and downstream markers of the Wnt signaling pathway (GSK3β and β-catenin) within subcutaneous inguinal white adipose tissue (iWAT), and visceral epididymal WAT (eWAT) depots at rest and in response to acute aerobic exercise.Methods: Male C57BL/6 mice (n = 40, 18 weeks of age) underwent 10 weeks of either a low-fat diet (LFD) or HFD. Within each diet group, mice were assigned to either remain sedentary (SED) or perform 2 h of endurance treadmill exercise at 15 m min−1 with 5° incline (EX), creating four groups: LFD + SED (N = 10), LFD + EX (N = 10), HFD + SED (N = 10), and HFD + EX (N = 10). Serum and WAT depots were collected 2 h post-exercise.Results: Serum sclerostin showed a diet-by-exercise interaction, reflecting HFD + EX mice having higher concentration than HFD + SED (+31%, p = 0.03), and LFD mice being unresponsive to exercise. iWAT sclerostin content decreased post-exercise in both 28 kDa (−31%, p = 0.04) and 30 kDa bands (−36%, main effect for exercise, p = 0.02). iWAT β-catenin (+44%, p = 0.03) and GSK3β content were higher in HFD mice compared to LFD (+128%, main effect for diet, p = 0.005). Monomeric sclerostin content was abolished in eWAT of HFD mice (−96%, main effect for diet, p &lt; 0.0001), was only detectable as a 30 kDa band in LFD mice and was unresponsive to exercise. β-catenin and GSK3β were both unresponsive to diet and exercise within eWAT.Conclusion: These results characterized sclerostin’s content to WAT depots in response to acute exercise, which appears to be specific to a reduction in iWAT and identified a differential regulation of sclerostin’s form/post-translational modifications depending on diet and WAT depot.
The effects of 4-Phenylbutyric acid on ER stress during mouse tooth development
Authors: Lee Eui-Seon , Aryal Yam Prasad , Kim Tae-Young , Pokharel Elina , Kim Ji-Youn , Yamamoto Hitoshi , An Chang-Hyeon , An Seo-Young , Jung Jae-Kwang , Lee Youngkyun , Ha Jung-Hong , Sohn Wern-Joo , Kim Jae-Young 
Published: January 2023

Introduction: During tooth development, proper protein folding and trafficking are significant processes as newly synthesized proteins proceed to form designated tissues. Endoplasmic reticulum (ER) stress occurs inevitably in tooth development as unfolded and misfolded proteins accumulate in ER. 4-Phenylbutyric acid (4PBA) is a FDA approved drug and known as a chemical chaperone which alleviates the ER stress. Recently, several studies showed that 4PBA performs therapeutic effects in some genetic diseases due to misfolding of proteins, metabolic related-diseases and apoptosis due to ER stress. However, the roles of 4PBA during odontogenesis are not elucidated. This study revealed the effects of 4PBA during molar development in mice.Methods: We employed in vitro organ cultivation and renal transplantation methods which would mimic the permanent tooth development in an infant period of human. The in vitro cultivated tooth germs and renal calcified teeth were examined by histology and immunohistochemical analysis.Results and Discussion: Our results revealed that treatment of 4PBA altered expression patterns of enamel knot related signaling molecules, and consequently affected cellular secretion and patterned formation of dental hard tissues including dentin and enamel during tooth morphogenesis. The alteration of ER stress by 4PBA treatment during organogenesis would suggest that proper ER stress is important for pattern formation during tooth development and morphogenesis, and 4PBA as a chemical chaperone would be one of the candidate molecules for dental and hard tissue regeneration.