bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and in vivo evaluation of paclitaxel-induced release of apoptotic biomarker ccCK18 to guide treatment optimization in ovarian cancer&nbsp;
Authors: Thaye Elien De , Vijver Koen Van de , Dorpe Jo Van , Vermeulen An , Bocxlaer Jan Van , Colin Pieter 
Published: October 2020

Abstract
Background: Cytokeratins hold potential as biomarkers due to their epithelial specificity, abundance and cleavage by caspases during apoptosis. We evaluated paclitaxel-induced circulating caspase-cleaved (cc) cytokeratin 18 (CK18) as potential apoptotic cell-death marker to guide treatment optimization in ovarian cancer.Methods: Six ovarian cancer cell lines (SK-OV-3, SK-OV-3lucIP1, Caov-3, NIH:OVCAR-3, PA-1 and PM-LGSOC-01) were exposed in vitro to paclitaxel (PTX, 0 to 1000 nM) for 24h. Extracellular levels of ccCK18 were measured until 5 days after drug exposure. Cell count and ccCK18 release data were analyzed using a phase-nonspecific pharmacodynamic model implemented in NONMEM®. PA-1 and SK-OV-3lucIP1 xenografted female SCID/Beige mice received a placebo or single dose of 50 mg/kg PTX intraperitoneally. Response to PTX was evaluated in vivo using tumor volume and released ccCK18 levels. Results: In vitro, the correlation between cell count and released ccCK18 levels was present in all cell lines (Spearman’s rank correlation coefficient > 0.64). Tumor volume and ccCK18 longitudinal dynamics were markedly different for controls and PTX-treated PA-1 xenografts with changes in ccCK18 release preceding changes in tumor volume. For SK-OV-3lucIP1 xenografts, no differences were found between controls and PTX-treated mice.Conclusions: An association between PTX-induced ccCK18 release and cell count was demonstrated in vitro. The in vivo study supported the presence of an early-apoptotic peak in ccCK18 levels compared to a later observed effect on tumor volume in PTX-sensitive xenografts. Given the heterogeneous character of ovarian cancer, application and implementation of ccCK18 in a clinical setting to optimize or personalize cancer treatment needs further refinement.
Virulent secondary metabolites of entomopathogenic bacteria genera, Xenorhabdus and Photorhabdus, inhibit phospholipase A2 to suppress host insect immunity
Authors: Mollah Md. Mahi Imam , Kim Yonggyun 
Published: October 2020

Abstract
Background: Xenorhabdus and Photorhabdus are entomopathogenic bacteria that cause septicemia and toxemia in insects. They produce secondary metabolites to induce host immunosuppression. Their metabolite compositions vary among bacterial species. Little is known about the relationship between metabolite compositions and the bacterial pathogenicity. The objective of this study was to compare pathogenicity and production of secondary metabolites of 14 bacterial isolates (species or strains) of Xenorhabdus and Photorhabdus. Results: All bacterial isolates exhibited insecticidal activities after hemocoelic injection to Spodoptera exigua (a lepidopteran insect) larvae, with median lethal doses ranging from 168.8 to 641.3 CFU per larva. Bacterial infection also led to immunosuppression by inhibiting eicosanoid biosynthesis. Bacterial culture broth was fractionated into four different organic extracts. All four organic extracts of each bacterial species exhibited insecticidal activities and resulted in immunosuppression. These organic extracts were subjected to GC-MS analysis which predicted 182 compounds, showing differential compositions for 14 bacteria isolates. There were positive correlations between total number of secondary metabolites produced by each bacterial culture broth and its bacterial pathogenicity based on immunosuppression and insecticidal activity. From these correlation results, 70 virulent compounds were selected from secondary metabolites of high virulent bacterial isolates by deducting those of low virulent bacterial isolates. These selected virulent compounds exhibited significant immunosuppressive activities by inhibiting eicosanoid biosynthesis. They also exhibited relatively high insecticidal activities. Conclusion: Virulence variation between Xenorhabdus and Photorhabdus is determined by their different compositions of secondary metabolites, of which PLA2 inhibitors play a crucial role.
Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults
Authors: Zhang Yuanyuan , Zhou Chun , Li Jianping , Zhang Yan , Xie Di , Liang Min , Wang Binyan , Song Yun , Wang Xiaobin , Huo Yong , Hou Fan Fan , Xu Xiping , Qin Xianhui 
Published: October 2020

Abstract
Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG <6.1mmol/L at baseline and ≥6.1 but <7.0mmol/L at the exit visit.Results: Over a median of 4.5 years follow-up, 1,549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95%CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95%CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) <10μmol/L (adjusted OR, 1.24; 95%CI: 1.10, 1.40 vs. ≥10μmol/L: adjusted OR, 1.03; 95%CI: 0.96, 1.10; P-interaction=0.007) or FG ≥5.9mmol/L (adjusted OR, 1.16; 95%CI: 1.07, 1.27 vs. <5.9mmol/L: adjusted OR, 1.00; 95%CI: 0.93, 1.08; P-interaction =0.009)Conclusions: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels.Clinical Trial Registration-URL: Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.
Efficacy of the Self-Mutual-Group model targeting quality of life improvement among empty-nest elderly: An intervention study
Authors: Zhang Chichen , Xue Yaqing , Cai Yuan , Lu Jiao , Zheng Xiao , Yuan Wenpei , Qian Yi 
Published: October 2020

Abstract
BackgroundThe “empty nest” family is becoming the main family pattern in China. Meanwhile, the health-related quality of life of empty-nest elderly is an increasing public health concern. This research aims to examine the effectiveness of Self-Mutual-Group (SMG) model in improving quality of life of the empty-nest elderly to provide a scientific evidence for improving their health.MethodsA prospective intervention study was conducted among empty-nest elderly in Taiyuan, Shanxi. Participants who met the inclusion criteria were assigned randomly to the intervention or control group. The intervention group received a seven-month SMG-based intervention. A participant’s quality of life was measured at the baseline and seven months after using the Short Form 36-Item Health Survey (SF-36).ResultsNo significant difference was found between the intervention and control groups in terms of participant characteristics at baseline (P > 0.05). After the intervention, participants’ scores on Mental Component Summary (MCS), Physical Component Summary (PCS), role emotional (RE), vitality (VT), social function (SF), mental health (MH) and general health (GH) increased significantly in the intervention group. Additionally, these scores differed significantly from those in the control group (P < 0.05).ConclusionThis study showed that the SMG-based health management is effective in improving quality of life among empty-nest elderly after seven months.Trial registrationStudy on the ‘SMG’ Health Management Model Based on Community Organization Theory among empty-nest elderly (ChiCTR1800015884). Registration date: 26-04-2018. Retrospectively registered.
Melatonin as an endogenous hormone to slow down the exhaustion of ovarian follicle reserve in mice–a novel insight into its roles in early folliculogenesis and ovarian aging
Authors: Yang Chan , Liu Qinghua , Chen Yingjun , Wang Xiaodong , Ran Zaohong , Fang Fang , Xiong Jiajun , Liu Guoshi , Li Xiang , Yang Liguo , Changjiu He 
Published: October 2020

Abstract
Previous studies have shown that long-term intake of exogenous melatonin can effectively delay ovarian aging, but the mechanism has not been fully elucidated. We observed that SNAT, the rate-limiting enzyme in the melatonin synthetic pathway, is localized in primordial and early follicle, and that granulosa cells isolated from follicle can synthesize melatonin. In vitro cultured neonatal mice ovaries with melatonin inhibited primordial follicle activation and early follicle growth. In vivo experiments further indicated that daily injections of melatonin to neonatal mice during the primordial follicle activation phase can reduce the number of activated follicles by inhibiting the PI3K-AKT-FOXO3 pathway; during the early follicle growth phase, injections of melatonin significantly suppressed early follicle growth and atresia, and transcriptome data showed that multiple pathways involved in folliculogenesis, including PI3K-AKT, were suppressed. Further, SNAT knockout in mice resulted in a significant increase in follicle activation and atresia, and eventually accelerated ovarian aging. We also demonstrated that prolonged high-dose melatonin intake had no obvious adverse effect on the health condition of mice. This study confirms that endogenous melatonin is involved in the regulation of ovarian aging, and reveals that melatonin delays ovarian aging by inhibiting primordial follicle activation, early follicle growth and atresia.
Identification and Characterization of TUBBY genes in developmental stages of Zea mays
Authors: Mejia Sendi , Shah Suhani , Abdelsalam Yara , Nimra Ali , Bhatt Munzir , Borges Daniela , Chen Joey , Dwamena George , Elcock Angel , Firrello Jason , Foster Anordia , James Josephine , Jenkins Delivrance , Khan Maheen , Lewis Adwoa , Manzanilla Ana , Morataya Melisa , Pendleton Shedonna , Quill Deanni , Zayas Orlando Rivera , Rosengarden Shannon , Scott Mornette , Suriel Meliss , Toussaint Wildine , Valencia Paula , Wadhwani Pragya , Zaib Arshia , Marco Cristina Fernandez , Monaco Marcela K. , Ware Doreen , Noutsos Christos 
Published: October 2020

Abstract
In this paper, we studied the organization and function of TUBBY Transcription Factor gene family in maize. Initially, using comparative approach, we discovered the Arabidopsis thaliana orthologs in Zea mays. We found in total 13 genes, 12 of which are orthologs and a unique paralog that exhibits the highest activity in maize. We studied the role of TUBBY gene family across different developmental stages using existing expression data, and discovered the binding motifs present in the promoter region of the genes.
Extensive genomic plasticity identified by anti-cancer Huaier therapy
Authors: Tanaka Manami , Tanaka Tomoo , Teng Fei , Lin Hong , Xu Chenying , Li Ning , Luo Zhu , Wei Ding , Lu Zhengxin 
Published: October 2020

Abstract
Clinical significance of anti-cancer effects of Huaier has been emphasized recently. We have proved that a broad spectrum of Huaier effects was based on the rescue of the disrupted Hippo signalling pathway, especially through the rescue of transcriptional dysregulation. We initiated clinical research for thorough understanding of mode of action by total RNA- and small non-coding RNA-sequencing. Here we provide the surprising genomic plasticity by Huaier observed in the time course of recovery from cancer. The extensive changes in RNA editing events were first observed, such as average 92,427 SNP variances per individual (22,688 in normal control). The subsequent changes in the process of translation and transcription resulted in the drastic changes in number of up/down-regulated transcripts. The ratio of the changes at maximum was 85% (23,210/27,447). With the advent of many novel sequences found in small nuclear RNAs and the consequent gene-silencing derived from miRNA-mediated post-transcriptional control, quantitative and qualitative changes of expression in transcriptional factors (mean 1,115/person) contributed to rescue dysregulated functions occurred in almost all required physiological functions for cancer recovery. The transcription control was demonstrated as functional lineage map between the core transcriptional factor and functionally linked transcripts, and the recovery could be clearly shown as the silencing of those massive changes in the end. The genetic alterations, especially related to the inhibition of NFκB and TGF-β signalling pathways showed significant effects on the improvement of prognosis. Thus, Huaier therapy contributes to cancer cell death with damaged tissue regeneration by extensive and systematic genomic modulations.
Multiple Endocrine Neoplasia Type 1 Combined With Papillary Thyroid Carcinoma and Nodular Goiter: A Case Report and Review of The Literature
Authors: Xu Jialu , Dong Su , Han Zhe , Sun Lele , Liu Jia 
Published: October 2020

Abstract
Introduction: This is the first report of multiple endocrine neoplasia type 1 (MEN1) combined with papillary thyroid carcinoma (PTC) and nodular goiter in China. MEN1 is a rare hereditary tumor syndrome inherited in an autosomal dominant manner and presenting mostly as tumors of the parathyroid, endocrine pancreas (such as gastrinoma) and anterior pituitary. However, PTC and nodular goiter were not previously regarded as components.Patient concerns: We present a 35-year-old woman with MEN1 accompanied with coinstantaneous PTC and nodular goiter.Diagnosis: The pathological diagnosis was PTC with cervical lymph node metastasis, nodular goiter, parathyroid cyst and adenomatoid hyperplasia. Genetic analysis was performed and a germ-line MEN1 gene mutation was detected.Interventions: The patient underwent unilateral lobectomy of the thyroid gland and surgical removal of the parathyroid tumors.Outcomes: After 6 months of follow-up, ultrasonic examination of the patient’s neck showed no abnormality. Serum calcium and parathyroid hormone levels were normal.Conclusion: This is the first experience of a case of MEN1 combined with PTC and nodular goiter in China. MEN1 syndrome may have predisposed the present patient to PTC and nodular goiter. PTC and/or nodular goiter may be new components of MEN1. More cases are required to confirm this association.
Establishment of A Rapid and Stable Infected System by Agrobacterium-Mediated Transformation of Germination Seeds in Diploid Strawberry.
Authors: Xu Peng-Hao , Gu Xiao-Jiao , Shen Yuan-Yue 
Published: October 2020

Abstract
Background Strawberry (Fragaria) is regarded as a model plant for both Rosaceae and non-climacteric fruit ripening. Although much progress has been made in identification of gene function using stable and transient genetic transformation systems in strawberry, the limitation is, more or less, are present. To this end, development of a rapid, efficient, and stable transformation system is required for strawberry research and breeding. Results Here, using diploid Hawaii-4 (Fragaria vesca) seeds and a reporter gene of CHLH (the H subunit of magnesium chelatase magnesium chelatase) key to chlorophyll synthesis, we first develop a rapid, efficient, and stable infected system by the Agrobacterium-mediated seed infection to silence the reporter gene, reaching an infection frequency with 28.3% through a series of optimization elements, including seed full imbibition and initial germination, shaking infection for 24 h, dark cultivation on MS medium for 3 d at 24 ℃, light culture on MS-Tim medium for 1 week at 24 ℃, and vector construction tagged with fluorescence label. Taken together, radicle-emergence germination seeds, appropriate Agrobacterium concentration and infection time are critical for successful infection, finally obtaining the infected kanamycin-resistant seedlings of T1 generation by infected wild seeds within 1 month and T2 generation-infected plants within 4 months. Conclusions The Agrobacterium-mediated infection of germinating seeds (AMTGS) in diploid strawberry (F. vesca) is first established, providing a useful tool for gene function identification and improved agronomic traits in strawberry.
Predictors of Radiographic Erosion and Joint Space Narrowing Progression in Patients with Early Rheumatoid Arthritis: A Cohort Study
Authors: Rydell Emil Per , Forslind Kristina , Nilsson Jan-Åke , Karlsson Magnus , Åkesson Kristina E , Jacobsson Lennart TH , Turesson Carl 
Published: October 2020

Abstract
Background Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately. Methods Consecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995–2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion- and JSN progression from inclusion to the 5-year follow-up were evaluated.Results Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion- and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking, high levels of cartilage oligomeric matrix protein (>12 U/L) and high baseline disease activity (DAS28 >5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion- and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥25kg/m2) was a significant negative predictor of JSN score progression (ß= -0.14, p= 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p= 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (>51 years), but not in younger women. The truncal: peripheral fat ratio was associated with less JSN score progression in women, but not in men. Conclusions Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.
In Vivo Assessment of Glutamine Anaplerosis into the TCA Cycle in Human Pre-malignant and Malignant Clonal Plasma Cells
Authors: Gonsalves Wilson , Jang Jin Sung , Jessen Erik , Hitosugi Taro , Evans Laura , Jevremovic Dragan , Petterson Xuan-Mai , Bush Alexander Graham , Gransee Jaimee , Anderson Emilie I , Kumar Shaji K , Sreekumaran K. 
Published: October 2020

Abstract
BackgroundOverexpression of c-Myc is required for the progression of pre-malignant plasma cells in monoclonal gammopathy of undetermined significance (MGUS) to malignant plasma cells in multiple myeloma (MM). c-Myc also increases glutamine anaplerosis into the tricarboxylic acid (TCA) cycle within cancer cells. Whether increased glutamine anaplerosis is associated with the progression of pre-malignant to malignant plasma cells is unknown.MethodsHuman volunteers (N = 7) and patients with MGUS (N = 11) and MM (N = 12) were prospectively recruited to undergo an intravenous infusion of 13C-labelled glutamine followed by a bone marrow aspiration to obtain bone marrow cells and plasma.ResultsDespite notable heterogeneity, stable isotope resolved metabolomics (SIRM) revealed that the mean 13C-labelled glutamine anaplerosis into the TCA cycle was higher in malignant compared to pre-malignant bone marrow plasma cells relative to the remainder of their paired bone marrow mononuclear cells. RNA sequencing demonstrated a higher relative mRNA expression of c-Myc and glutamine transporters such as ASCT2 and SN2 in malignant compared to pre-malignant bone marrow plasma cells. Finally, higher quantitative levels of TCA cycle intermediates in the bone marrow plasma differentiated MM from MGUS patients.ConclusionMeasurement of the in vivo activity of glutamine anaplerosis into the TCA cycle provides novel insight into the metabolic changes associated with the transformation of pre-malignant plasma cells in MGUS to malignant plasma cells in MM.
Few-Layer Graphene Induces Both Primary and Secondary Genotoxicity in in Vitro Alveolar Barrier Models
Authors: Burgum Michael John , Cl Martin JD , Evans Stephen J , Hondow Nicole , Tarat Afshin , Jenkins Gareth J , Doak Shareen H 
Published: October 2020

Abstract
Background: Toxicological evaluation of engineered nanomaterials (ENMs) is essential for occupational health and safety, particularly where bulk manufactured ENMs such as few-layer graphene (FLG) are concerned. Additionally, there is a necessity to develop advanced in vitro models when testing ENMs to provide a physiologically relevant alternative to invasive animal experimentation. The aim of this study was to determine the genotoxicity of non-functionalised (neutral), amine- and carboxyl-functionalised FLG upon both human-transformed type-I (TT1) alveolar epithelial cell monocultures, as well as co-cultures of TT1 and differentiated THP-1 monocytes (d.THP-1 (macrophages)). Results: In monocultures, TT1 and d.THP-1 macrophages showed a statistically significant (p<0.05) cytotoxic response with each ENM following 24-hour exposures. Monoculture genotoxicity measured by the in vitro cytokinesis blocked micronucleus (CBMN) assay revealed significant (p<0.05) micronuclei induction at 8µg/ml for amine- and carboxyl-FLG. Transmission electron microscopy (TEM) revealed ENMs were internalised by TT1 cells within membrane-bound vesicles. In the co-cultures, ENMs induced genotoxicity in the absence of cytotoxic effects. Co-cultures pre-exposed to 1.5mM N-acetylcysteine (NAC), showed baseline levels of micronuclei induction, indicating that the genotoxicity observed was driven by oxidative stress. Conclusions: Therefore, FLG genotoxicity when examined in monocultures, results in primary-indirect DNA damage; whereas co-cultured cells reveal secondary mechanisms of DNA damage.