bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folic Acid Can Reduce Hyperhomocysteinemia-induced Vascular Damage by Immune/Inflammatory Response in Spontaneously Hypertensive Rats
Authors: Zhang Lihua , li Zhongliang , Xing Changcheng , Gao Ning , Cao Ping , Hui Qingcheng , Yun Lin , Xu Rui 
Published: May 2020

Abstract
Background

Hypertension associated with hyperhomocysteinemia (HHcy) is correlated with a high risk of vascular diseases. However, the mechanisms of HHcy-associated hypertensive vascular damage and the efficacy of folic acid (FA) as a treatment have not been fully elucidated. The aim of the present study was to evaluate the role of immune/inflammatory molecules and oxidizing factors in HHcy-associated hypertensive vascular damage, and to observe the intervention effect of FA on the two vascular injury factors.
Methods

Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were administered DL-Hcy intraperitoneally to mimic HHcy and hypertension associated with HHcy for 12 weeks. WKYs and SHRs were randomized into WKY group, HHcy group, SHR group, SHR + HHcy group and SHR + HHcy + FA group. Mean tail artery blood pressure, plasma Hcy, serum SOD and MDA of rats in each group were compared. The thoracic aorta and bilateral carotid artery of rats were harvested for morphometric and immunostaining analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of immune/inflammatory molecules such as TNF-α, IL-6, NF-κB p65/Rela and NF-κB2 and oxidative factors such as Nox2 and Nox4.
Results

We found that vascular inflammatory factors of vascular adhesion protein-1 (VAP-1), interleukin-6 (IL-6), and nuclear factor-κ-gene binding (NF-κB) p65/Rela in HHcy-associated hypertensive rats were significantly higher than those in SHRs (P༜0.05). While the oxidative stress indicators of Nox2 and Nox4 in HHcy-associated hypertensive rats were not significantly higher than those in SHRs (P༞0.05). Compared with SHRs, FA intervention in HHcy-associated hypertensive rats significantly increased serum superoxide dismutase (SOD) levels (P = 0.000) and significantly reduced vascular inflammatory factors of IL-6 and NF-κB p65/Rela (P༜0.05), but did not significantly change the oxidative stress indicators of Nox2 and Nox4 (P༞0.05).
Conclusions

HHcy-induced immune/inflammatory response plays a dominant role in vascular damage of HHcy-associated hypertensive rats. In addition to reducing the negative effects of HHcy, FA might involve unique antioxidant effects and inhibition of immune/inflammatory overreaction for HHcy-associated hypertensive rats.
Retrospective cohort study of nanoparticle albumin-bound paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment in patients with advanced gastric cancer
Authors: Okunaka Mashiro , Kotani Daisuke , Demachi Ken , Kawazoe Akihito , Yoshino Takayuki , Kawasaki Toshikatsu , Shitara Kohei 
Published: May 2020

Abstract
Background Nanoparticle albumin-bound paclitaxel (nab-PTX) has shown non-inferiority to paclitaxel (PTX) as second-line therapy for advanced gastric cancer (AGC) with fewer infusion-related reactions. The efficacy and safety of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial; however, there is no randomized trial comparing this regimen with PTX plus RAM in patients with AGC. This retrospective study aimed to investigate the efficacy and safety of nab-PTX plus RAM versus PTX plus RAM in patients with AGC. Methods This study included patients with AGC who received nab-PTX plus RAM from September 2017 to January 2019 or PTX plus RAM from June 2015 to August 2017 as second-line chemotherapy in our hospital. Results A total of 113 and 138 patients who received nab-PTX plus RAM and PTX plus RAM, respectively, were analyzed. Median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]: 3.4–4.3) in the nab-PTX plus RAM group and 3.9 months (95% CI: 3.1–4.7) in the PTX plus RAM group (hazard ratio [HR]: 1.08; 95% CI: 0.83–1.40; P = 0.573). Median overall survival (OS) was 10.9 months (95% CI: 9.3–12.7) in the nab-PTX plus RAM group and 10.3 months (95% CI: 8.5–12.0) in the PTX plus RAM group (hazard ratio: 0.82; 95% CI: 0.61–1.10; P = 0.188). In patients with moderate/massive ascites, favorable outcomes for progression-free survival were observed in the nab-PTX plus RAM group compared with the PTX plus RAM group. Although anemia and fatigue (any grade) were more frequent in the nab-PTX plus RAM group, discontinuation of study treatment was not increased in the nab-PTX plus RAM group. There was no occurrence of hypersensitivity reaction in the nab-PTX plus RAM group, while two patients (1.4%) experienced grade 3 hypersensitivity reactions in the PTX plus RAM group. Conclusions The combination of nab-PTX plus RAM showed a similar efficacy and safety profile to PTX plus RAM as second-line treatment for patients with AGC.
Development and Validation of Food Frequency Questionnaire for Food and Nutrient Intake of Adults in Butajira, Southern Ethiopia
Authors: Feyesa Ilili , Endris Bilal S , Habtemariam Esete , Hassen Hamid Y , Gebreyesus Seifu H 
Published: May 2020

Abstract
Background: To date, there is no culture-specific and validated Food Frequency Questionnaire (FFQ) available in Ethiopia. We developed a FFQ and evaluated its validity as compared to estimates of a food group and nutrient intakes derived from two 24-Hour Dietary Recalls (24-HRs).Method: The FFQ has a total of 89 food items. A total of 105 adults aged 20–65 years participated in this study. Wilcoxon- signed rank test, Spearman’s correlation, Cross-classification, kappa, and Bland-Altman analysis were used to validate food group intakes and nutrients derived from FFQ against two 24-HRs.Results: Mean energy and macronutrient intakes obtained from the FFQ were significantly higher than those obtained from the mean of two 24-HRs. For energy and macronutrients, the correlation between two instruments ranged from 0.05 (total fat) to 0.32 (carbohydrate). Whereas, for micronutrients it ranged from 0.1 (calcium) to 0.49 (vitamin B1). Visual inspection of the Bland-Altman plots for both energy and macronutrients shows no consistent trend across the intake values. For the majority of the food groups, no significant difference was observed in median intake of foods and nutrients between 24-HRs and FFQ. Correlation coefficients for food groups ranged from 0.12 (egg) to 0.78 (legumes). The FFQ showed a fair classification agreement with the 24-HRs for cereals, legumes, and roots and tubers intakes. A systematic trend of overestimation for roots and tubers and under estimation of beverage intakes at higher values was observed when we used FFQ.Conclusion: The FFQ is valid to assess and rank individuals in terms of intakes of most food groups according to high and low intake categories. However, estimates of roots and tuber and beverages should be interpreted with caution.
Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice
Authors: He Jia , Yuan Renyikun , Cui Xiaolan , Cui Yushun , Han Shan , Wang Qin-Qin , Chen Yangling , Huang Liting , Yang Shilin , Xu Qiongming , Zhao Yonghui , Gao Hongwei 
Published: May 2020

Abstract
Background Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.Methods The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP- induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (Ribavirin or Ceftriaxone Sodium Injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA). Proteins expression was quantified by western blotting.Results The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.Conclusion Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.
Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in Letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect
Authors: Azouz Asmaa A. , Ali Sara E. , Abd-Elsalam Reham M. , Emam Shimaa R. , Galal Mona K. , Elmosalamy Sherif H. , Alsherbiny Muhammad , Hassan Bardes B. , Li Chun Guang , Badawy Shymaa A. El 
Published: May 2020

Abstract
Background Complementary remedies such as the Chinese herb ‘Sheng Ma’ (Black cohosh; Actaea racemose ‘AR’) are being sought to surmount the shortcomings of conventional hormonal and surgical therapies developed in the treatment of polycystic ovary syndrome (PCOS). However, the AR hepatotoxicity urges a cautionary warning to be labelled on its products as recommended by the United States Pharmacopeia where 4 out of 7 hepatotoxic cases in Sweden were possibly associated with black cohosh products.Methods We investigated the efficacy, safety and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality, oxidative response in the hyperandrogenism-induced PCOS alongside with holistic profiling of its arsenal of secondary metabolites using UPLC-Qtof-MS. A well-established rat model using oral letrozole, daily, for 21 days was employed then the rats received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, apoptosis, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated.Results Beneficial effects were exerted by AR in PCOS rats via the improved antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, curtailed percentage of apoptotic cells and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells. Notably, AR combination with vitamin C was not only more effective to reverse the dysregulated levels of testosterone, luteinising hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer, while the combination regulated both ovarian and hepatic MDA and GSH levels with a histologic improvement noticed in livers and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.Conclusion This study demonstrated the benefit of the combination between AR and vitamin C in mitigating the reproductive and metabolic disorders of PCOS with the elimination of AR hepatotoxic risk.
Abnormal Expression and Prognostic Significance of EPB41L1 in Kidney Renal Clear Cell Carcinoma Based on Data Mining
Authors: Liang Taotao , Sang Siyao , Shao Qi , Deng Zhichao , Wang Ting , Kang Qiao-zhen 
Published: May 2020

Abstract
Background: EPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remains to be investigated.Methods: In this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub-groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC were analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. Co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them were visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser.Results: The results indicated that EPB41L1 was down-expressed in KIRC, leading to a poor prognosis. Moreover, there is a mutation in the FERM domain of EPB41L1, but it has no significant effect on the prognosis of KIRC. The co-expressed genes of EPB41L1 was associated with cell adhesion. Further analysis suggested that EPB41L1 and amyloid beta precursor protein (APP) were coordinated to regulated cancer cell adhesion, thereby increasing the incidence of cancer cell metastasis and tumor invasion.Conclusions: In summary, EPB41L1 is constantly down-expressed in KIRC tissues, resulting a poor prognosis. Therefore, we suggest that it can be an effective biomarker for the diagnosis of KIRC.
Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure
Authors: Jiang Ting , Xia Geng , Yang Bo , Zhang Hong-wei , Yin Yue-shan , Tang Cheng-wei , Yang Jin-hui 
Published: May 2020

Abstract
Background

Endotoxemia based on liver failure has been reported to be related to the worse clinical outcomes, but its management remains unsatisfactory. The addition of bone marrow mesenchymal stem cells (BMSCs) could promote the recovery of liver function and increase the survival with the liver failure. However, little is known about the potential of cell therapy with endotoxemia based on liver failure.
Methods

BMSCs were isolated from rats, and their morphology, differentiation potential, surface markers, and cell cycle were assayed. Thioacetamide-induced acute liver failure rats were randomized to groups with or without BMSCs. During the experiment, survival was recorded. Diamine oxidase (DAO), endotoxin, interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-α) and tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), histology, and western blot. Bromodeoxynucleoside uracil (BrdU) incorporation assay was performed to observe the migration of BMSCs. The intestinal epithelial differentiation of BMSCs was induced by co culture with small intestinal crypt in rats (IEC-6). Immunofluorescence was used to analyze the expression of intestinal endothelial markers. Western blot analysis was further performed to examine the differentiation effect when inhibiting the phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.
Results

BrdU-traced BMSCs targeted migrate to intestinal injury sites. Mortality was significantly decreased and intestinal damage was repaired following BMSCs transplantation. Proteomics revealed higher expression of DAO, endotoxin, IL-6 and TNF-α in the model animals, but these changes were reversed after BMSCs transplantation. In the in vitro study, the intestinal epithelial differentiation of BMSCs was exhibited following co-culture. Moreover, the blocking of PI3K/AKT/mTOR signal pathway inhibited this differentiation.
Conclusions

These evidences indicate that BMSCs eliminate endotoxemia and reduce mortality in the animal model of acute liver failure by reducing intestine damage.
Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis
Authors: Yu Dingding , Zhao Yiming , Hu Yonghao , Kong Dejun , Jin Wang , Qin Yafei , Zhang Baoren , Li Xiang , Hao Jingpeng , Wang Hongda , Li Guangming , Wang Hao 
Published: May 2020

Abstract
Background

We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1low-ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis.
Methods

BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1low-ERCs) and glucocorticoid-treated ERCs (DKK1high-ERCs) were injected (1 million/mouse/day, i.v.) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction.
Results

It was found that DKK1low-ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2, CD4+CD25+FOXP3+Treg, and CD68+CD206+macrophages in spleens were also significantly upregulated in DKK1low-ERC group (p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1low-ERC group (p < 0.01 vs. other groups).
Conclusions

DKK1low-ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.
Impact of using non-rebreathing mask in patients with respiratory failure
Authors: Li Chao-Jui , Lin Yan-Ren , Chen Chien-Chih , Lin Xin-Hong , Chuang Po-Chun 
Published: May 2020

Abstract
Background
Liberal oxygen therapy might increase the mortality rate of patients. Non-rebreathing mask (NRM) is a high-flow, non-invasive oxygen device that can provide oxygen concentration up to 95%. This study aimed to determine the impact of using NRM in patients with respiratory failure.
Methods
This retrospective cohort study was conducted in four medical institutions in Taiwan. Data were extracted from the Chang Gung Research Database between January 2010 and December 2016. The association between mortality and NRM use in patients with respiratory failure in the emergency department was analysed. Before receiving ventilator support, patients were divided into the NRM treatment and no NRM treatment groups. A 1:4 propensity score matching was conducted. Regarding the duration of NRM use, treatments were grouped as 0 hour, 0–1 hour, 1–2 hours, and > 2 hours.
Results
A total of 18749 patients were included, with 1074 using NRM. After the 1:4 propensity score matching, 1028 patients using NRM and 4112 patients not using NRM were analysed. The 72-hour and 30-day mortality rates were 14.8%, 14.1%, 10.4%, and 11.3% and 29.1%, 28.5%, 27.5%, and 35.5% in the 0 hour, 0–1 hour, 1–2 hour, and > 2 hour treatment groups, respectively. Patients with respiratory failure due to pulmonary disease using NRM (> 2 hours) for a prolonged period had a higher mortality rate than patients not using NRM (OR: 1.4, 95% CI: 1.06–1.74).
Conclusions
Prolonged use of NRM (> 2 hours) in patients with respiratory failure due to pulmonary disease possibly results in an increased mortality rate.
Antimicrobial effects of Black Soldier Fly and Yellow Mealworm fats and their impact on gut microbiota of growing rabbits
Authors: Dabbou Sihem , Ferrocino Ilario , Gasco Laura , Schiavone Achille , Trocino Angela , Xiccato Gerolamo , Lajusticia Ana Cristina Barroeta , Maione Sandra , Soglia Dominga , Biasato Ilaria , Cocolin Luca , Gai Francesco , Nucera Michele Daniele 
Published: May 2020

Abstract
Background
The study aimed to evaluate the in vitro antimicrobial activities of two types of insect fats extracted from black soldier fly larvae (HI, Hermetia illucens L.) and yellow mealworm larvae (TM, Tenebrio molitor L.) and their effects as dietary replacement of soybean oil (S) on caecal fermentation pattern, and faecal and caecal microbiota in rabbits.
Results
A total of 120 weaned rabbits were randomly allotted to 3 dietary treatments (40 rabbits/group): a control diet (C diet) containing 1.5% of S and two experimental diets (HID and TMD) where S was totally substituted by HI or TM fats. Regarding the in vitro antimicrobial activities, HI and TM fats did not show any effects on Salmonella growth. Yersinia enterocolitica showed lower growth when challenged with insect fats than the controls. The insect fat supplementation in rabbit diets increased the contents of the caecal volatile fatty acids when compared to the control group. A metataxonomic approach was adopted to investigate the shift in the microbial composition as a function of the dietary insect fat supplementation. The microbiota did not show a clear separation as a function of the inclusion, even if a specific microbial signature was observed. Indeed, HI and TM fat supplementation enriched the presence of Akkermansia that was found to be correlated with NH3-N concentration. An increase in Ruminococcus, which can improve the immune response of the host, was also observed.
Conclusions
This study confirms the potential of HI and TM fats as antibacterial feed ingredients with a positive influence on the rabbit caecal microbiota, thus supporting the possibility of including HI and TM fats in rabbit diets.