bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pleiotropic effects of prebiotic galacto-oligosaccharides on the aging gut
Authors: Arnold Jason W , Roach Jeffery , Fabela Salvador , Moorfield Emily , Ding Shengli , Blue Eric , Dagher Suzanne , Magness Scott , Tamayo Rita , Bruno-Barcena Jose , Azcarate-Peril M. Andrea 
Published: February 2020

Abstract
Background: Prebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the mechanistic impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects (“leaky gut”). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges, since these interventions are common and relevant in older adults. Finally, we assessed the ability of colonic organoids to reproduce in vivo responses to GOS.Results: Old animals had a distinct microbiome characterized by lower diversity, increased ratios of non-saccharolytic versus saccharolytic bacteria and lower abundance of O-Glycosyl hydrolases . GOS treatment increased abundance of non-saccharolytic ( Akkermansia muciniphila ) and saccharolytic bacteria (species of Bacteroides and Lactobacillus ), and increased the abundance of β-galactosidases and β-glucosidases in young and old animals . Clyndamicin treatment reduced the abundance of beneficial bacteria including Bifidobacterium and Lactobacillus , while increasing Akkermansia, Clostridium, Coprococcus, Enterococcus, Bacillus, Bacteroides, and Paenibacillus . Prebiotics impacted the effects of the antibiotics decreasing the abundance of Akkermansia in the GOS-antibiotic groups compared to the control-antibiotics groups. GOS reduced the age-associated increased intestinal permeability via increased MUC2 expression and mucus biosynthesis. T ranscriptomics analysis of colon from old animals fed GOS diets showed increased expression of genes involved in small molecule metabolic processes and specifically the respirasome, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced expression of binding-related genes and the galectin gene Lgals1 , a β-galactosyl-binding lectin that bridges molecules by their sugar moieties, forming a signaling and adhesion network. Further analysis showed higher expression levels of genes in focal adhesion, PI3K-Akt and ECM-receptor interaction pathways. GOS reduced the expression of TNF  in old animals, and altered serum levels of inflammatory biomarkers IL-6, IL-17, IP-10 and Eotaxin. Stools from young mice exhibiting variable bifidogenic response to GOS, injected into colon organoids in the presence of prebiotics, reproduced the response and non-response phenotypes.Conclusions: GOS modulation of intestinal homeostasis likely occurs through direct GOS-host interactions via modulation of host gene expression and mucus production, as well as through interactions mediated by the gut microbiota that result in increased or restored saccharolytic potential.
Isolation frequency of medically important fungi and fluconazole resistant of Candida sp from hospital cockroaches.
Authors: Mloka Doreen Anna , Bwire George M , Mwambete Kenndy 
Published: February 2020

Abstract
BackgroundCockroaches are common pests in homes and hospitals. They are known to cause allergic reactions in certain individuals and have found to be potential vectors for various bacterial and parasitic pathogens. This study assessed the potential of hospital cockroaches to act as vectors of medically important fungal pathogens on their external surfaces.MethodsCockroaches were captured from the main Intensive care unit (ICU), burn unit, adult surgical wards , pediatric oncology wards, intern hostel kitchen and the central kitchen of a national referral teaching hospital in Tanzania. Normal saline washings from the external surface of cockroaches were cultured on standard mycological media to facilitate isolation and identification of medically important molds and yeasts. Susceptibility of Candida sp isolates to fluconazole was tested using the CLSI M27-A3 microdilution method.ResultsAt total of 72 cockroaches were captured from various sites of the hospital between February and March 2015. All cockroaches captured were shown to carry medically importance fungi. A total of 956 medically important fungi were isolated, 57.9 % were Candida sp., 23.2%, Aspergillus sp. , 3.1% Cladosporium sp., 1.8% Rhizopus sp., 1.2 % Geotrichum sp., 0.9 % Pencillum sp. , 0.7% Alternaria sp, 0.6 % Fusarium sp , 0.3% Mucor sp and 10.1% others. Aspergillus fumigatus (50.0%) was the most commonly isolated followed by Aspergillus niger ( 15.8%) among the Aspergillus isolates.Over 16.3 % of the Candida isolates not intrinsically resistant to fluconazole showed resistance to this drug.mResistance was most frequently found in Candidapseudotropicalis (23.8%) and Candida glabarata (20.0%) and least in isolates of Candida albicans ( 6.3%). ConclusionThe external surfaces of cockroaches from this hospital may act as reservoirs of medically important opportunistic fungi exhibiting resistance to fluconazole.
Low serum betaine levels as a potential biomarker for type 2 diabetes mellitus in patients with coronary artery disease
Authors: Guo Fei , Qiu Xueting , Zhu Yuanting , Tan Zhirong , Ouyang Dongsheng , Li Zhenyu 
Published: February 2020

Abstract
Background Dietary betaine intake was reported to associate with improved metabolic profile in type 2 diabetes (T2D). However, the role of circulating betaine in coronary artery disease (CAD) patients with T2D is still unknown. This study aimed to investigate the potential role of serum betaine as a potential biomarker for T2D risk in CAD patients. Methods Total 307 subjects were enrolled with 165 CAD patients (57 with T2D and 108 without) and 142 age and sex matched controls (CON). Fasting serum betaine were detected using liquid chromatography tandem mass spectrometry. Results Serum betaine were lower in simple CAD patients compared with healthy controls, and were further decreased in CAD patients with T2D. Betaine was inversely associated with fasting glucose. Subjects in the highest betaine tertile group had lower triglycerides, total cholesterol and low-density lipoprotein as well was lower percentage of CAD and T2D. Increased betaine in CAD was independently associated with low risk of T2D. Furthermore, betaine was a potential diagnostic marker in distinguishing simple CAD from CAD with T2D. Conclusion Low levels of betaine are associated with increased risk of CAD and T2D in CAD, and could be a biomarker for predicting T2D in CAD.
Prion protein-mediated calcium level alteration governs neuronal cell damage through AMPK-autophagy flux
Authors: Moon Ji-Hong , Park Sang-Youel 
Published: February 2020

Abstract
Background The distinctive molecular structure of the prion protein, PrPsc, is established only in mammals with infectious prion diseases. Prion protein characterizes either the transmissible pathogen itself or a primary constituent of the disease. Our report suggested that prion-mediated neuronal cell death is triggered by the autophagy flux. However, the alteration of intracellular calcium levels, AMPK activity in prion models has not been described. This study is focused on the effect of the changes in intracellular calcium levels on AMPK/autophagy flux pathway and PrP (106–126)-induced neurotoxicity. Methods Western blot and Immunocytochemistry was used to detect AMPK and autophagy-related protein expression. Flow cytometry and a TdT-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay were used to detect the percentage of apoptotic cells. Calcium measurement was employed using fluo-4 by confocal microscope. Results We examined the effect of calcium homeostasis alterations induced by human prion protein on the autophagy flux in neuronal cells. Treatment with human prion protein increased the intracellular calcium concentration and induced cell death in primary neurons as well as in a neuronal cell line. Using pharmacological inhibitors, we showed that the L-type calcium channel is involved in the cellular entry of calcium ions. Inhibition of calcium uptake prevented autophagic cell death and reduction in AMP-activated protein kinase (AMPK) activity induced by human prion protein. Conclusion Our data demonstrated that prion protein-mediated calcium inflow plays a pivotal role in prion protein-induced autophagic cell death, and reduction in AMPK activity in neurons. Altogether, our results suggest that calcium influx might play a critical role in neurodegenerative diseases, including prion diseases.
Chemosensitization of doxorubicin against lung cancer by nature borneol, involvement of TRPM8-regulated calcium mobilization
Authors: Lai Haoqiang , Liu Chang , Lin Wenwei , Chen tf , Hong An 
Published: February 2020

Abstract
Background Lung cancer possesses high mortality rate and tolerances to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that found to facilitate the bioavailability of drugs. In this study, we attempted to investigate effects of NB on the chemosensitivity in A549 cells and try to elucidate its therapeutic target. Methods The effects of NB on chemosensitivity in A549 cells was examined by MTT assay. The mechanism studies were evaluated by flow cytometry and western blotting assay. Surface plasmon resonance (SPR) and LC-MS combined analysis (MS-SPRi) was performed to elucidate the candidate target of NB contributes to this synergism. The chemosensitizing capacity of NB in vivo was conducted in nude mice bearing A549 tumors. Results NB pretreatment sensitizes A549 cells to low dosage of DOX, leading to a 15.7% to 41.5% increase in apoptosis, which is corelated with ERK and AKT inactivation but activation of phosphor-p38MAPK, -JNK and p53. Furthermore, this synergism depends on reactive oxygen species (ROS) generation. The MS-SPRi analysis reveals that the transient receptor potential melastatin-8 (TRPM8) is the interaction target of NB in potentiating DOX killing potency. Genetically knock down of TRPM8 significantly suppress the chemosensitizing effects of NB with the involvement of inhibiting ROS generation through restraining calcium mobilization. Moreover, pretreatment of NB synergistically enhanced the anticancer effects of DOX to delay tumor progression in vivo. Conclusions These results suggest that TRPM8 may be a valid therapeutic target in the potential application of NB serves as a chemosensitizer for lung cancer treatment.
Circular RNA MTO1 inhibits the proliferation and invasion of ovarian cancer cells through the miR-182-5p/KLF15 axis
Authors: Wang Ning , Cao Qin-Xue , Tian Jun , Ren Lu , Cheng Hai-Ling , Yang Shao-Qin 
Published: February 2020

Abstract
Background: Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs and have been shown to play important roles in a variety of physiological processes. Recently, dysregulation of circRNAs has been identified in many types of cancers. In this study, we analyzed the expression profile and biological functions of circMTO1 in ovarian cancer. Materials and methods: Cell proliferation and invasion were assessed by CCK-8 and transwell assay, respectively. The RT-qPCR analysis was performed to measure mRNA levels of circMTO1 and miR-182-5p. The western blot was used to detect KLF15 protein levels. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A. Results: We demonstrated that circMTO1 was down-regulated in ovarian cancer tissues and cell lines. Up-regulation of circMTO1 inhibited proliferation and invasion of ovarian cancer cells while down-regulation of circMTO1 promoted these processes. Mechanistically, we showed that circMTO1 sponged miR-182-5p to support KLF15 expression, eventually leading to inhibition of ovarian cancer progression. Conclusions: Our study suggested circMTO1 as a novel biomarker and therapeutic target for ovarian cancer treatment.
SIRT1 promotes EMT, migration and invasion by regulating mTORC1/4E-BP1 in colorectal cancer
Authors: Liu Peifeng , Chen Xiaojing , Qin Shaolan , Zhou Yan , Yu Bo , Luo Yang , Xie Yuexia , Liu Hongmei , Zhong Ming , Kong Xianming 
Published: February 2020

Abstract
Background Metastasis, rather than primary tumors, was accounted for the most cases of cancer death in colorectal cancer(CRC). The understanding of the underlying mechanism associated with tumor metastasis would improve the patient’s miserable fate. SIRT1 has been identified to play a role in tumorigenesis and progression of malignant tumors, especially in keeping the characteristics of cancer stem cells(CSCs) in CRC. This study was conducted to investigate the role of SIRT1 in the regulation of metastasis and the underlying mechanism in colorectal cancer. Methods We detected the expression of SIRT1 in 42 metastatic CRC patients. The relationship between SIRT1 and time to metastasis was also analyzed. Then the SIRT1 activity was regulated to investigate the liver metastasis in BALB/c mice. SIRT1 was knocked down to evaluate the effect on migration and invasion. Besides, exogenetic SIRT1 to assess the motile ability by wound healing assay and transwell assay. We then further explored the underlying mechanism. Results SIRT1 was overexpressed in 67% CRC metastatic patients and associated with reduced time to metastasis. High SIRT1 activity by resveratrol was companied with more liver metastasis in vivo. SIRT1 deficiency increased E-cadherin, while reduced Vimentin and Snail, attenuated migration and invasion significantly in CT26 and SW620 cells. Meanwhile, the exogenetic SIRT1 induced epithelial–mesenchymal transition (EMT) and elevated the migratory ability in SW480 cells. Further studies demonstrated that mTORC1 related genes were elevated while 4E-BP1 decayed by SIRT1 overexpression. The promotion of metastasis induced by SIRT1 overexpression could be abolished by mTOR inhibition, while the stemness of cells was not changed. Conclusions Collectively, our findings illustrated that SIRT1 was a functional regulator in the promotion of metastasis in CRC via mTORC1-4E-BP1 axis. SIRT1 was a potential independent prognostic factor of CRC metastatic patients after tumor resection, which provided a promising treatment target in CRC.
Mannitol and renal graft injury in patients undergoing deceased donor renal transplantation – A randomized controlled clinical trial
Authors: Reiterer Christian , Hu Karin , Sljivic Samir , von Sonnenburg Markus Falkner , Fleischmann Edith , Kainz Alexander , Kabon Barbara 
Published: February 2020

Abstract
BackgroundIschaemia/reperfusion (I/R) injury is associated with renal tissue damage during deceased donor renal transplantation. Evidence is weak regarding the effect of mannitol attenuating I/R injury during graft reperfusion in renal transplant recipients. We tested the effect of mannitol to reduce renal graft injury represented by 16 serum biomarkers, which are involved in different relevant pathophysiological pathways. Our primary outcome were differences in biomarker concentrations between the mannitol and the placebo group 24 hours after graft reperfusion. Additionally, to account for biomarker concentrations before transplantation, a linear mixed model was applied.Methods4 patients undergoing deceased donor renal transplantation were randomly assigned at the Medical University of Vienna to receive either 20% mannitol or 0.9% NaCl placebo solution before and after graft reperfusion. 16 serum biomarkers (MMP1, CHI3L1, CCL2, MMP8, HGF, GH, FGF23, Tie2, VCAM1, TNFR1, IGFBP7, IL18, NGAL, Endostatin, CystC, KIM1) were measured preoperatively and 24 hours after graft reperfusion using Luminex assays and ELISA.Results16 patients in each group were analysed. Tie2 differed 24 hours after graft reperfusion between both groups (p = 0.011). Change of log2 transformed concentration levels over time differed significantly in four biomarkers (VCAM1,Endostatin, KIM1, GH; p=0.007; p = 0.013; p = 0.004; p = 0.033; respectively) out of 16 between both groups.ConclusionOur study showed insufficient effects of mannitol on I/R injury in patients undergoing deceased renal transplantation. Thus, we do not support the routinely use of mannitol to attenuate I/R injury.
Post Caesarean Wound sepsis and associated factors among patients attending a rural regional referral hospital in Western Uganda: A cross-sectional study
Authors: Muhumuza Ismael , Lavingia Abdulrahman Zeinul , Tayebwa Bekson , Ahmed Ahmed Abdulhussein , Koriow Farhiya Mohammed , Tetty Victor Otieno , Nzabandora Emmanuel , Almenares Ubarnel , Fonseca Ivan Bonet , Kyobutungi Victo , Turyagumanawe John , Atuheire Collins , Ssebuwufu Robinson 
Published: February 2020

Abstract
Background : Post-caesarean wound sepsis is among the most common problem for patients who undergo caesarean section. It remains a common and widespread problem contributing to morbidity and mortality; this could be due to an increase in antimicrobial resistance. Determining the burden of wound sepsis and common bacterial pathogens can provide solution to prevent incidence and establish microbiological mapping. Aim: To determine prevalence, identify factors, common bacterial pathogens from post-caesarean wounds and antibacterial susceptibility pattern at Hoima Regional Referral Hospital. Methods : A cross-sectional study was conducted among post-caesarean mothers attending Hoima Regional Referral Hospital. Consecutive enrolment of 303 participants who consented to participate was done. Structured questionnaires were used to collect data on associated factors and wound swabs were done prior to bacterial culture. Antibacterial susceptibility pattern of isolated bacterial pathogens was determined by Kirby Bauer disc diffusion method. Data was analyzed using Stata 14.2. Results : The wound sepsis rate was 16.8%. Being educated, multiple vaginal examination, hygiene, previous caesarean sections and HIV seropositivity were all significantly and positively associated with post-caesarean wound sepsis (p<0.05). The most implicated bacteria was Staphylococcus aureus and was most susceptible to ciprofloxacin. Resistance was most exhibited against ciprofloxacin, gentamycin, ceftriaxone and cotrimoxazole especially by coliforms. Conclusions. The rate of caesarean wound sepsis is high at Hoima Regional Referral Hospital . Being educated, multiple vaginal examination, hygiene, previous caesarean sections and HIV seropositivity are possible risk factors for the condition. Staphylococcus aureus is the commonest organism isolated from exudates of septic wounds after caesarean section. Awareness amongst health workers and patients about these major factors is necessary so that management can be directed. Rational use of antibiotics by health workers is paramount to combat resistance in this setting.
Development of a rapid detection method for Trichomonas vaginalis based on loop-mediated isothermal amplification targeting adhesion protein 65
Authors: Li Yuhua , Li Haoran , Song Xiaoxiao , Zhang Hao , Duan Yujuan , Luo Chengyang , Wang Bingli , Ji Sifan , Wang Shuai , Xie Qing , Zhang Zhenchao 
Published: February 2020

Abstract
Background: Trichomoniasis resulting from Trichomonas vaginalis (T. vaginalis) has been considered as a commonly seen disease with the transmission way of sex. At present, the detection methods of T. vaginalis mainly include wet mount microscopy, culture, PCR, immunofluorescence and ELISA. However, all of these detection methods exist shortcomings.Methods: In this study, a loop-mediated isothermal amplification (LAMP) assay that targeted the species-specific sequence of adhesion protein 65 (AP65) gene had been conducted to detect T. vaginalis. The optimum reaction system and conditions were optimized in this rapid detection method.Results: The results of sensitivity analysis showed that the LAMP assay targeting the AP65 gene was 1000 times more sensitive than the nested PCR targeting the actin gene commonly used for detection of T. vaginalis, and the detecting limitation of the former was 10 trichomonad. Moreover, the amplification of the target gene AP65 by LAMP assay exhibited high specificity and the product was exclusively from T. vaginalis. The detection technique of LAMP did not exhibit cross-reactivity with the common pathogens of Trichinella spiralis, Toxoplasma gondii, Escherichia coli, Candida albicans, Staphylococcus aureus, Haemophilus.Conclusions: According to the present study, the LAMP assay with the target of AP65 gene, was suitable for the early diagnosis of T. vaginalis infections. Consequently, the LAMP assay was proposed by the current study as a point-of-care examination and an alternative molecular tool which exhibited the potential value in the treatment, control and prevention of trichomoniasis transmission and relevant complication.
Zoonotic leishmaniasis and heartworm disease in Italy: changing epidemiological scenarios and future perspectives
Authors: Mendoza-Roldan Jairo , Benelli Giovanni , Panarese Rossella , Iatta Roberta , Furlanello Tommaso , Beugnet Frederic , Zatelli Andrea , Otranto Domenico 
Published: February 2020

Abstract
Background: For long time, canine leishmaniosis (CanL) was considered endemic in the southern, central, and insular regions of Italy, whereas heartworm disease (HW) by Dirofilaria immitis in the northern region and in the swampy Po valley. Following the reports of new foci of both diseases, in this study we update the distribution patterns and occurrence of new foci of CanL and HW discussing the main drivers for the changes in the epidemiology of these two important zoonotic canine vector-borne diseases.Methods: Based on the statistical analyses of serological assays (n=90,633) on CanL and HW performed by reference diagnostic centres in Italy over a ten-year period (2009–2019), the distribution patterns of both diseases were herein presented along with the occurrence of new foci.Results: Results highlighted the changing distribution patterns of CanL vs HW disease in Italy. CanL is now also endemic in the northern regions and HW has endemic foci in central and southern regions and islands. Significant differences in CanL and HW prevalence among the study macroareas were detected. The overall prevalence of CanL was 28.2% in Southern Italy and Islands, 29.6% in Central Italy and 21.6% in Northern Italy and that of HW of 2.83% in northern Italy, 7.75% in central Italy and 4.97% in southern Italy and islands. HW prevalence significantly varied over years (χ2=108.401, d.f.=10, p<0.0001), gradually increasing from 0.77% in 2009 to values ranging from 5.19-8.47% in 2016-2017.Conclusions: The new epidemiological scenarios have been discussed according to a range of factors (e.g. environmental modifications, occurrence of competent insect vectors, transportation of infected animals to non-endemic areas, chemoprophylaxis or vector preventative measures), which may affect the current distribution. Overall, results advocate for epidemiological surveillance programs, more focussed preventative and control measures even in areas where few or none cases of both diseases have been diagnosed.