bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the mechanism of action of Sanzi formula in intervening colorectal adenoma by targeting intestinal flora and intestinal metabolism
Authors: Shang Jingyu , Guo Hong , Li Jie , Li Zhongyi , Yan Zhanpeng , Wei Lanfu , Hua Yongzhi , Lin Lin , Tian Yaozhou 
Published: September 2022

BackgroundSanzi formula (SZF) is a kind of Chinese herbal compound that has a certain effect on the prevention and treatment of colorectal adenoma (CRA), which can prevent and control the process of CRA-cancer transformation. In this study, we explored the mechanism of action of SZF in anti-CRA using 16S rRNA sequencing and metabolomics technology.MethodsMice were randomly divided into three groups: Control group, Apcmin/+ model group, and SZF treatment group. Except for the Control group, which used C57BL/6 J mice, the remaining two groups used Apcmin/+ mice. The Control group and Apcmin/+ model group were treated with ultrapure water by gavage, while the SZF treatment group was treated with SZF for 12 weeks. During this period, the physical changes of mice in each group were observed. The gut microbiota was determined by high-throughput sequencing of the 16S rRNA gene, and LC-ESI-MS/MS was used for colorectal metabolomics analysis.ResultsSequencing of the 16S rRNA gut flora yielded 10,256 operational taxonomic units and metabolomic analysis obtained a total of 366 differential metabolites. The intestinal flora analysis showed that SZF could improve intestinal flora disorders in Apcmin/+ mice. For instance, beneficial bacteria such as Gastranaerophilales significantly increased and harmful bacteria such as Angelakisella, Dubosiella, Muribaculum, and Erysipelotrichaceae UCG-003 substantially decreased after the SZF intervention. In addition, metabolomic data analysis demonstrated that SZF also improved the colorectal metabolic profile of Apcmin/+ mice. In Apcmin/+ mice, metabolites such as Anserine and Ectoine were typically increased after SZF intervention; in contrast, metabolites such as Taurocholic acid, Taurochenodesoxycholic acid, Hyocholic acid, Cholic acid, and Tauro-alpha-muricholic acid showed noteworthy reductions. Metabolic flora association analysis indicated that 13 differential flora and 11 differential metabolites were associated.ConclusionSZF affects the abundance of specific intestinal flora and regulates intestinal flora disorders, improves colorectal-specific metabolites, and ameliorates intestinal metabolic disorders to prevent and treat CRA. Furthermore, the application of intestinal flora and colorectal metabolomics association analysis offers new strategies to reveal the mechanism of action of herbal medicines for the treatment of intestinal diseases.
Chicken IgY reduces the risk of Pseudomonas aeruginosa urinary tract infections in a murine model
Authors: Schwartz Franziska A. , Christophersen Lars , Thomsen Kim , Baekdal Sarah , Pals Bendixen Maria , Jørgensen Mette , Bull Rasmussen Ida Kirstine , Laulund Anne Sofie , Høiby Niels , Moser Claus 
Published: September 2022

IntroductionUrinary tract infections (UTIs) withPseudomonas aeruginosaare a severe problem in disposed patients in modern healthcare.Pseudomonas aeruginosaestablishes recalcitrant biofilm infections and can develop antibiotic resistance. Gargling with avian egg yolk anti-Pseudomonasantibodies (IgY) has shown clinical effect in preventing onset of chronicP. aeruginosalung infections in patients with cystic fibrosis (CF). Therefore, we speculated whether passive intravesically administered IgY immunotherapy could be a novel strategy againstP. aeruginosaUTIs.AimTo evaluate if prophylactic repurposing of anti-PseudomonasIgY can prevent UTIs withP. aeruginosain a UTI mouse model.Materials and methodsIn vitro,P. aeruginosa(PAO1 and PAO3) was mixed with increasing concentrations of specific anti-PseudomonasIgY (sIgY) or non-specific control IgY (cIgY) and/or freshly isolated human neutrophils. Bacterial growth was evaluated by the optical density at 600 nm.In vivo,viaa temporary transurethral catheter, 10-week-old female Balb/c mice were intravesically infected with 50 ml of a bacterial suspension and sIgY, cIgY, or isotonic NaCl. IgY and NaCl were either co-instilled with the bacteria, or instilled prophylactically, 30 min prior to infection. The animals were euthanized 20 h after infection. Vesical bacteriology was quantified, and cytokine expression in the bladder homogenate was measured by multiplex cytokine assay.ResultsIn vitro, sIgY concentrations above 2.5% reduced bacterial growth in a dose-dependent manner.In vivo, a UTI lasting for minimum 7 days was established by installing 5 × 106colony-forming units (CFU) ofP. aeruginosaPAO1. sIgY reduced vesical bacterial load if co-installed withP. aeruginosaPAO1. Prophylactic sIgY and cIgY reduced bacterial load when compared to isotonic NaCl. CXCL2 and G-CSF were both increased in infected bladders compared to non-infected controls which had non-detectable levels. Co-installation of sIgY and bacteria nearly completely inhibited the inflammatory response. However, the cytokine levels in the bladder did not change after prophylactic administration of sIgY or cIgY.ConclusionProphylactic sIgY significantly reduces the amount of bacteria in the bladder in a mouse model ofP. aeruginosacystitis and may serve as a novel non-antibiotic strategy in preventingP. aeruginosaUTIs.
Hizikia fusiforme functional oil (HFFO) prevents neuroinflammation and memory deficits evoked by lipopolysaccharide/aluminum trichloride in zebrafish
Authors: Nie Ying-Ying , Zhou Long-Jian , Li Yan-Mei , Yang Wen-Cong , Liu Ya-Yue , Yang Zhi-You , Ma Xiao-Xiang , Zhang Yong-Ping , Hong Peng-Zhi , Zhang Yi 
Published: September 2022

BackgroundOxidative stress, cholinergic deficiency, and neuroinflammation are hallmarks of most neurodegenerative disorders (NDs). Lipids play an important role in brain development and proper functioning. Marine-derived lipids have shown good memory-improving potentials, especially those from fish and microalgae. The cultivated macroalga Hizikia fusiforme is healthy food and shows benefits to memory, but the study is rare on the brain healthy value of its oil. Previously, we had reported that the Hizikia fusiforme functional oil (HFFO) contains arachidonic acid, 11,14,17-eicosatrienoic acid, phytol, and other molecules displaying in vitro acetylcholinesterase inhibitory and nitroxide scavenging activity; however, the in vivo effect remains unclear. In this study, we further investigated its potential effects against lipopolysaccharides (LPS)- or aluminum trichloride (AlCl3)-induced memory deficiency in zebrafish and its drug-related properties in silica.MethodsWe established memory deficit models in zebrafish by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS) (75 ng) or aluminum trichloride (AlCl3) (21 μg), and assessed their behaviors in the T-maze test. The interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), acetylcholine (ACh), and malondialdehyde (MDA) levels were measured 24 h after the LPS/AlCl3 injection as markers of inflammation, cholinergic activity, and oxidative stress. Furthermore, the interaction of two main components, 11,14,17-eicosatrienoic acid and phytol, was investigated by molecular docking, with the important anti-inflammatory targets nuclear factor kappa B (NF-κB) and cyclooxygenase 2 (COX-2). Specifically, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of HFFO were studied by ADMETlab.ResultsThe results showed that HFFO reduced cognitive deficits in zebrafish T-maze induced by LPS/AlCl3. While the LPS/AlCl3 treatment increased MDA content, lowered ACh levels in the zebrafish brain, and elevated levels of central and peripheral proinflammatory cytokines, these effects were reversed by 100 mg/kg HFFO except for MDA. Moreover, 11,14,17-eicosatrienoic acid and phytol showed a good affinity with NF-κB, COX-2, and HFFO exhibited acceptable drug-likeness and ADMET profiles in general.ConclusionCollectively, this study's findings suggest HFFO as a potent neuroprotectant, potentially valuable for the prevention of memory impairment caused by cholinergic deficiency and neuroinflammation.
Long- and short-term fluctuations compared for several organ systems across sleep stages
Authors: Zschocke Johannes , Bartsch Ronny P. , Glos Martin , Penzel Thomas , Mikolajczyk Rafael , Kantelhardt Jan W. 
Published: September 2022

Some details of cardiovascular and cardio-respiratory regulation and their changes during different sleep stages remain still unknown. In this paper we compared the fluctuations of heart rate, pulse rate, respiration frequency, and pulse transit times as well as EEG alpha-band power on time scales from 6 to 200 s during different sleep stages in order to better understand regulatory pathways. The five considered time series were derived from ECG, photoplethysmogram, nasal air flow, and central electrode EEG measurements from full-night polysomnography recordings of 246 subjects with suspected sleep disorders. We applied detrended fluctuation analysis, distinguishing between short-term (6–16 s) and long-term (50–200 s) correlations, i.e., scaling behavior characterized by the fluctuation exponents α1 and α2 related with parasympathetic and sympathetic control, respectively. While heart rate (and pulse rate) are characterized by sex and age-dependent short-term correlations, their long-term correlations exhibit the well-known sleep stage dependence: weak long-term correlations during non-REM sleep and pronounced long-term correlations during REM sleep and wakefulness. In contrast, pulse transit times, which are believed to be mainly affected by blood pressure and arterial stiffness, do not show differences between short-term and long-term exponents. This is in constrast to previous results for blood pressure time series, where α1 was much larger than α2, and therefore questions a very close relation between pulse transit times and blood pressure values. Nevertheless, very similar sleep-stage dependent differences are observed for the long-term fluctuation exponent α2 in all considered signals including EEG alpha-band power. In conclusion, we found that the observed fluctuation exponents are very robust and hardly modified by body mass index, alcohol consumption, smoking, or sleep disorders. The long-term fluctuations of all observed systems seem to be modulated by patterns following sleep stages generated in the brain and thus regulated in a similar manner, while short-term regulations differ between the organ systems. Deviations from the reported dependence in any of the signals should be indicative of problems in the function of the particular organ system or its control mechanisms.
Safety and efficacy of low-dose and long-course tirofiban in large hemispheric infarction
Authors: Hu Yinqin , Xiao Qian , Shi Zhizhen , Hou Yangbo , Chen Zhen , Cheng Jiwei , Li Guoyi 
Published: September 2022

BackgroundThe clinical efficacy and safety of tirofiban in the treatment of large hemispheric infarction (LHI) remain controversial.MethodsThis study prospectively enrolled patients with acute LHI who were admitted to Putuo Hospital affiliated with Shanghai University of Traditional Chinese Medicine from June 2021 to December 2021. The patients were randomly assigned to the tirofiban group [3–4 μg/(kg·h)] or control group (clopidogrel 75 mg/d).ResultsA total of 71 patients with acute LHI were selected: 36 in the tirofiban group and 35 in the control group. The reduction of the NIHSS score in the tirofiban group was 2.92 ± 9.31 at discharge, and that of the control group was −3.23 ± 12.06 (p = 0.021, OR, 0.006; 95% CI, 0.004–0.008). Six patients (16.7%) in tirofiban group and 14 patients (40%) in control group died during hospitalization (p = 0.029, OR, 0.300; 95% CI, 0.099–0.908). There was significant difference in Modified Rankin Scale (mRS) 5–6 scores at 90 days between the two groups (p = 0.023, OR, 0.327; 95% CI, 0.124–0.867). However, there was no significant difference in mRS 0–1 (p = 0.321, OR, 0.972; 95% CI, 0.920–1.027), mRS 2 (p = 0.572, OR, 2.00; 95% CI, 0.173–23.109), mRS 3 (p = 0.225, OR, 2.214; 95% CI, 0.601–8.161), or mRS 4(p = 0.284, OR, 1.859; 95% CI, 0.593–5.825) scores between the two groups. There was no difference in symptomatic intracranial hemorrhage (p = 0.29, OR, 0.305; 95% CI, 0.030–3.081), asymptomatic intracranial hemorrhage (p = 0.123, OR, 0.284; 95% CI, 0.053–1.518). There was a significant difference in systemic bleeding events during hospitalization (p = 0.044, OR, 0.309; 95% CI, 0.096–1.000).ConclusionsLow-dose and long-course tirofiban treatment may significantly improve the early neurological function and reduce the in-hospital mortality in LHI patients. Meanwhile, tirofiban does not increase the risk of any type of bleeding events.
Factors associated with artificial airway retention after skull base chordoma resection: A retrospective cohort study
Authors: Fu Yuxuan , Yu Yun , Cui Yidan , Wang Jing , Ma Bo , Jian Minyu , Yao Jingxin , Jing Longnian , Bai Jiwei , Han Ruquan 
Published: September 2022

BackgroundChordoma is a malignant bone and soft tissue tumor derived from embryonic notochord remnants, and skull base chordoma accounts for ~1/3 of all chordoma cases. Skull base chordoma is closely related to the brainstem and cranial nerves and has a high recurrence rate. The purpose of this study was to investigate the influence of the timing of tracheal extubation on perioperative pulmonary complications. We also aimed to explore predictors of postoperative artificial airway (AA) retention in patients with skull base chordoma.MethodsThis was a single-center, retrospective cohort study. The study population included all skull base chordoma patients undergoing surgical treatment between January 2019 and December 2021 at Beijing Tiantan Hospital. The primary outcome was the incidence of postoperative pulmonary complications. Several patient characteristics were evaluated for potential associations with AA retention.ResultsA total of 310 patients with skull base chordoma were enrolled. The frequency of AA retention after surgery for skull base chordoma was 30.97%. The incidence of postoperative pulmonary complications was much lower in those without AA retention (3.74 vs. 39.58%, P &lt; 0.001). Factors with the highest point estimates for the odds of AA retention included body mass index, cranial nerve involvement, maximum tumor diameter, operative method, hemorrhage volume, operative duration and intraoperative mechanical ventilation duration.ConclusionsIn this retrospective cohort study, most of the factors associated with postoperative airway retention were closely related to the patient's tumor characteristics. These data demonstrate that respiratory management in patients with skull base chordoma remains an ongoing concern.
Higher Circulating Vitamin D Levels Are Associated With Decreased Migraine Risk: A Mendelian Randomization Study
Authors: Niu Peng-Peng , Wang Xue , Xu Yu-Ming 
Published: September 2022

BackgroundEvidence showed the supplementation of vitamin D might have beneficial effects for migraine patients. We aimed to investigate the causal effects of serum vitamin D levels on migraine risk using two-sample Mendelian randomization (MR) method.MethodsA total of 184 independent genetic instruments for serum vitamin D levels were selected from a study in 417,580 Europeans from UK biobank. Six variants from an independent study were obtained to perform replication analysis. Summary-level data for migraine were obtained from three studies with 48,975 migraine cases, 28,852 migraine cases and 10,536 migraine cases, respectively.ResultsThe estimated odds ratios (ORs) per standard deviation increase in circulating vitamin D levels based on the three migraine datasets were 0.948 (95% CI = 0.883–1.016, p = 0.133), 0.902 (95% confidence intervals [CI] = 0.825–0.986, p = 0.023), and 0.880 (95% CI = 0.786–0.984, p = 0.025), respectively. Using pooled migraine summary data with no sample overlap, MR analysis showed per standard deviation increase in circulating vitamin D levels was significantly associated with a decreased migraine risk (OR = 0.916, 95% CI = 0.859–0.977, p = 0.008). Multivariable MR analyses, sensitivity analyses and replication analysis confirmed the association. MR analyses showed similar estimates for migraine with aura and migraine without aura but with wider 95% CIs. Mediation analysis showed the effect of vitamin D on migraine risk via pathway of serum calcium was corresponding to an OR of 1.003 (95% CI = 1.001–1.005) and a proportion mediated of 3.42%. The reverse MR analysis showed migraine might not affect vitamin D levels.ConclusionThis two-sample MR study showed genetically determined increased circulating vitamin D levels are associated with decreased migraine risk. The effect seems consistent across different migraine subtypes. In addition, the role of serum calcium in mediating the association between vitamin D and migraine is negligible. Future large well-designed randomized trials are warranted to assess the effects of vitamin D supplementation for migraine patients, especially in those with vitamin D deficiency.
Non-alcoholic fatty liver disease and dairy products consumption: Results from FASA Persian cohort study
Authors: Keshavarz Zahra , Rahimlou Mehran , Farjam Mojtaba , Homayounfar Reza , Khodadost Mahmoud , Abdollahi Ashkan , Tabrizi Reza 
Published: September 2022

Background/objectivesThere are limited data on the association between dairy products consumption and nonalcoholic fatty liver disease (NAFLD). This study was conducted to evaluate the association between total intake of different dairy products and fatty liver index (FLI), a marker of subclinical fatty liver.MethodsA total of 7,540 adults were included in this population-based cohort study. Dairy products consumption was evaluated by a validated interview questionnaire for food intake frequency. The FLI was calculated using the standard formula. Liver enzyme levels, lipid profiles, glycemic profiles and demographic characteristics were recorded for all participants. Univariate and multiple logistic regression models were used to respectively assess the mean percentage difference of mean FLI and odds ratios (ORs) for subclinical NAFLD across quantiles of dairy consumption.ResultsThe mean age of all participants was 48.81 ± 9.631 years. FLI measurements for men and women were 26.71 ± 23.39 and 39.99 ± 26.64 respectively, which was significantly higher in women (P &lt; 0.05). Multiple logistic regression analysis demonstrated that the amount of milk consumption was an independent preventive predictor of FLI (OR = 0.96; 95% CI: 0.94–0.99), conversely, it did not predict higher levels of liver enzymes. In term of cheese intake, participants in the third tertile of cheese intake had significantly lower FLI than lower tertiles (P = 0.01). However, there wasn't any significant association between cheese intake and the odds of FLI in the multivariate model (P &gt; 0.05). We didn't find any significant association between yogurt consumption and NAFLD indicators (P &gt; 0.05).ConclusionHigher milk consumption was inversely associated with FLI. However, there wasn't any significant association between other types of dairy products and NAFLD indicators.
In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma
Authors: Echeverría Cesar , Martin Aldo , Simon Felipe , Salas Cristian O. , Nazal Mariajesus , Varela Diego , Pérez-Castro Ramón A. , Santibanez Juan F. , Valdés-Valdés Ricardo O. , Forero-Doria Oscar , Echeverría Javier 
Published: September 2022

Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.
Cost-effectiveness analysis of trastuzumab deruxtecan versus trastuzumab emtansine for HER2-positive breast cancer
Authors: Yang Jiangping , Han Jiaqi , Zhang Yalan , Muhetaer Muhelisa , Chen Nianyong , Yan Xi 
Published: September 2022

Background: The DESTINY-Breast03 clinical trial demonstrated that trastuzumab deruxtecan (T-DXd) outperformed trastuzumab emtansine (T-DM1) in progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Considering the excessive cost of antibody-drug conjugates, the clinical value of T-DXd must be assessed by both its efficacy and cost. We compared the cost-effectiveness of T-DXd and T-DM1 for patients with HER2-positive mBC pretreated with anti-HER2 antibodies and a taxane from the perspectives of the United States (US) and China.Methods: A comprehensive Markov model based on the DESTINY-Breast03 phase III randomized clinical trial was used to compared the cost and effectiveness of T-DXd and T-DM1 for HER2-positive mBC. Data on direct medical cost and utilities were collected from published literatures. The recorded data included the costs, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER) and incremental net-health benefit (INHB). Sensitivity analysis was conducted to measure the potential uncertainty due to parameter variability. Additional subgroup cost-effectiveness analysis was performed.Results: Treatment of HER2-positive mBC with T-DXd gained 0.73 QALYs compared with T-DM1 strategy. The incremental cost was $59,942 in the US, with an ICER of $ 82,112/QALY and an INHB of 0.33 QALYs, respectively. In China, the incremental cost of T-DXd versus T-DM1 was $222,680, with an ICER of $305,041/QALY and a negative INHB of -5.18 QALYs. At willingness-to-pay (WTP) threshold of $150,000/QALY in the US and $37,653/QALY in China, the probability of T-DXd as the dominant option was 77.5 and 0.1%, respectively. The unit price of T-DXd greatly influenced the results according to one-way sensitivity analysis. To meet the 50% or 90% chance of being cost-effective, the estimated cost of T-DXd would need to be less than $17.24/mg and $12.06/mg in China, respectively.Conclusion: T-DXd is more cost-effective than T-DM1 for patients with HER2-positive mBC in the US, but not in China at current drug prices.