bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling
Authors: Zhang Xiao-Ning , Yang Kai-Di , Chen Cong , He Zhi-Cheng , Wang Qiang-Hu , Feng Hua , Lv Sheng-Qing , Wang Yan , Mao Min , Liu Qing , Tan Yao-Yao , Wang Wen-Ying , Li Tian-Ran , Che Lin-Rong , Qin Zhong-Yi , Wu Ling-Xiang , Luo Min , Luo Chun-Hua , Liu Yu-Qi , Yin Wen , Wang Chao , Guo Hai-Tao , Li Qing-Rui , Wang Bin , Chen Wei , Wang Shuang , Shi Yu , Bian Xiu-Wu , Ping Yi-Fang 
Published: July 2021

AbstractGlioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.
Degradation of lipid droplets by chimeric autophagy-tethering compounds
Authors: Fu Yuhua , Chen Ningxie , Wang Ziying , Luo Shouqing , Ding Yu , Lu Boxun 
Published: July 2021

AbstractDegrading pathogenic proteins by degrader technologies such as PROTACs (proteolysis-targeting chimeras) provides promising therapeutic strategies, but selective degradation of non-protein pathogenic biomolecules has been challenging. Here, we demonstrate a novel strategy to degrade non-protein biomolecules by autophagy-tethering compounds (ATTECs), using lipid droplets (LDs) as an exemplar target. LDs are ubiquitous cellular structures storing lipids and could be degraded by autophagy. We hypothesized that compounds interacting with both the LDs and the key autophagosome protein LC3 may enhance autophagic degradation of LDs. We designed and synthesized such compounds by connecting LC3-binding molecules to LD-binding probes via a linker. These compounds were capable of clearing LDs almost completely and rescued LD-related phenotypes in cells and in two independent mouse models with hepatic lipidosis. We further confirmed that the mechanism of action of these compounds was mediated through LC3 and autophagic degradation. Our proof-of-concept study demonstrates the capability of degrading LDs by ATTECs. Conceptually, this strategy could be applied to other protein and non-protein targets.
Viral vector gene delivery of the novel chaperone protein SRCP1 to modify insoluble protein in in vitro and in vivo models of ALS
Authors: Luecke Ian W. , Lin Gloria , Santarriaga Stephanie , Scaglione K. Matthew , Ebert Allison D. 
Published: July 2021

AbstractProtein misfolding and aggregation are shared features of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and protein quality control disruption contributes to neuronal toxicity. Therefore, reducing protein aggregation could hold therapeutic potential. We previously identified a novel chaperone protein, serine-rich chaperone protein 1 (SRCP1), that effectively prevents protein aggregation in cell culture and zebrafish models of Huntington’s disease. Here we tested whether this benefit extends to aggregated proteins found in ALS. We used viral-mediated expression of SRCP1 in in vitro and in vivo models of ALS. We found that SRCP1 reduced insoluble SOD1 protein levels in HEK293T cells overexpressing either the A4V or G93R mutant SOD1. However, the reduction of insoluble protein was not observed in either mutant C9orf72 or SOD1 ALS iPSC-derived motor neurons infected with a lentivirus expressing SRCP1. SOD1-G93A ALS mice injected with AAV-SRCP1 showed a small but significant reduction in insoluble and soluble SOD1 in both the brain and spinal cord, but SRCP1 expression did not improve mouse survival. These data indicate that SRCP1 likely reduces insoluble protein burden in a protein and/or context-dependent manner indicating a need for additional insight into SRCP1 function and therapeutic potential.
Whole genome survey of big cats (Genus: Panthera) identifies novel microsatellites of utility in conservation genetic study
Authors: Hyun Jee Yun , Pandey Puneet , Kim Kyung Seok , Chon Alvin , Jeong Daecheol , Bhak Jong , Yu Mihyeon , Song Hye Kyung , Singh Randeep , Min Mi-Sook , Goyal Surendra Prakash , Bayarkhagva Damdingiin , Marchenkova Taisia , Vitkalova Anna , Lee Hang 
Published: July 2021

AbstractBig cats (Genus: Panthera) are among the most threatened mammal groups of the world, owing to hunting, habitat loss, and illegal transnational trade. Conservation genetic studies and effective curbs on poaching are important for the conservation of these charismatic apex predators. A limited number of microsatellite markers exists for Panthera species and researchers often cross-amplify domestic cat microsatellites to study these species. We conducted data mining of seven Panthera genome sequences to discover microsatellites for conservation genetic studies of four threatened big cat species. A total of 32 polymorphic microsatellite loci were identified in silico and tested with 152 big cats, and were found polymorphic in most of the tested species. We propose a set of 12 novel microsatellite markers for use in conservation genetics and wildlife forensic investigations of big cat species. Cumulatively, these markers have a high discriminatory power of one in a million for unrelated individuals and one in a thousand for siblings. Similar PCR conditions of these markers increase the prospects of achieving efficient multiplex PCR assays. This study is a pioneering attempt to synthesise genome wide microsatellite markers for big cats.
Physical processes controlling the diurnal cycle of convective storms in the Western Ghats
Authors: Krishna U. V. Murali , Das Subrata Kumar , Deshpande Sachin M. , Pandithurai G. 
Published: July 2021

AbstractDiurnal variation of convective storms (CSs) during monsoon season and associated physical mechanisms are significantly important for accurate forecast of short-time and extreme precipitation. The diurnal cycle of CSs is investigated using ground-based X-band radar, Tropical Rainfall Measuring Mission Precipitation Radar, and reanalysis data during the summer monsoon (June–September of 2014) over complex mountain terrain of Western Ghats, India. Diurnally, CSs show a bimodal distribution in the coastal areas, but this bimodality became weak along the upslope regions and on the mountain top. The first occurrence mode of CSs is in the afternoon–evening hours, while the second peak is in the early-morning hours. The diurnal cycle’s intensity varies with location, such that it reaches maximum in the afternoon–evening hours and early morning on the mountain top and coastal areas, respectively. Two possible mechanisms are proposed for the observed diurnal variation in CSs (a) the radiative cooling effect and (b) the surface wind convergence induced by the interaction between land-sea breeze, local topography and large-scale monsoon winds. It is also observed that the CSs developed on the mountain top during afternoon–evening hours are deeper than those along the coast. The higher moisture in the lower- and mid-troposphere, higher instability and strong upward motion facilitate deeper CSs during afternoon–evening hours.
The ammonia oxidizing bacterium Nitrosomonas eutropha blocks T helper 2 cell polarization via the anti-inflammatory cytokine IL-10
Authors: Maura Damien , Elmekki Nazik , Goddard C. Alex 
Published: July 2021

AbstractThe prevalence of atopic diseases has been steadily increasing since the mid twentieth century, a rise that has been linked to modern hygienic lifestyles that limit exposure to microbes and immune system maturation. Overactive type 2 CD4+ helper T (Th2) cells are known to be closely associated with atopy and represent a key target for treatment. In this study, we present an initial characterization of ammonia oxidizing bacteria (AOB) Nitrosomonas eutropha D23, an environmental microbe that is not associated with human pathology, and show AOB effectively suppress the polarization of Th2 cells and production of Th2-associated cytokines (IL-5, IL-13, and IL-4) by human peripheral blood mononuclear cells (PBMC). We show that AOB inhibit Th2 cell polarization not through Th1-mediated suppression, but rather through mechanisms involving the anti-inflammatory cytokine IL-10 and the potential inhibition of dendritic cells, as evidenced by a reduction in Major Histocompatibility Complex Class II (MHC II) and CD86 expression following AOB treatment. This is the first report of immunomodulatory properties of AOB, and provides initial support for the development of AOB as a potential therapeutic for atopic diseases.
A novel index-based decision support toolkit for safe reopening following a generalized lockdown in low and middle-income countries
Authors: Shonchoy Abu S. , Ishtiaq Khandker S. , Talukder Sajedul , Ahmed Nasar U. , Chowdhury Rajiv 
Published: July 2021

AbstractWhile the effectiveness of lockdowns to reduce Coronavirus Disease-2019 (COVID-19) transmission is well established, uncertainties remain on the lifting principles of these restrictive interventions. World Health Organization recommends case positive rate of 5% or lower as a threshold for safe reopening. However, inadequate testing capacity limits the applicability of this recommendation, especially in the low-income and middle-income countries (LMICs). To develop a practical reopening strategy for LMICs, in this study, we first identify the optimal timing of safe reopening by exploring accessible epidemiological data of 24 countries during the initial COVID-19 surge. We find that a safe opening can occur two weeks after the crossover of daily infection and recovery rates while maintaining a negative trend in daily new cases. Epidemiologic SIRM model-based example simulation supports our findings. Finally, we develop an easily interpretable large-scale reopening (LSR) index, which is an evidence-based toolkit—to guide/inform reopening decision for LMICs.
Phytochemical composition and antioxidant properties of methanolic extracts of whole and dehulled Bambara groundnut (Vigna subterranea) seeds
Authors: Adedayo Bukola C. , Anyasi Tonna A. , Taylor Malcolm J. C. , Rautenbauch Fanie , Le Roes-Hill Marilize , Jideani Victoria A. 
Published: July 2021

AbstractThe distribution of phytochemicals and their contribution to antioxidant potentials in whole and dehulled Bambara groundnut (BGN) seeds was evaluated. Whole BGN seeds were sorted using the testa and hilium colour and further grouped into whole and dehulled BGN seeds. Extractions of both whole and dehulled BGN seeds was done using methanol and the extracts assayed for total phenolics (TPC), flavanol, flavonol, anthocyanin content, oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP). Methanolic extract of whole BGN seed exhibited higher flavanol and flavonol content as well as significantly higher in-vitro antioxidant activities than dehulled BGN seeds. The TPC of whole BGN seed extract ranged from 3.6 to 11.0 GAE/g, while that of dehulled BGN ranged from 2.7 to 3.2 GAE/g. Identification of phenolics in whole and dehulled BGN seed extract using UPLC-qTOF-MS, revealed the presence of monoterpenoids (iridoids), phenolic acids, flavonoids and lignans. Bivariate correlations showed anthocyanin demonstrated weak positive correlation between flavanol, flavonol and ORAC for whole BGN seed extract; and negative correlation between flavanol, TPC, FRAP and ORAC for dehulled BGN. Aside the effect of dehulling, whole BGN seeds exhibited the presence of phytochemicals with beneficial properties for food and industrial application.
Impact of plasma 5-hydroxyindoleacetic acid, a serotonin metabolite, on clinical outcome in septic shock, and its effect on vascular permeability
Authors: Tanaka Takeshi , Mori Masahiko , Sekino Motohiro , Higashijima Ushio , Takaki Masahiro , Yamashita Yoshiro , Kakiuchi Satoshi , Tashiro Masato , Morimoto Konosuke , Tasaki Osamu , Izumikawa Koichi 
Published: July 2021

AbstractSeptic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO2:FiO2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability.
Exploratory and territorial behavior in a reintroduced population of Iberian lynx
Authors: Rueda Carmen , Jiménez José , Palacios María Jesús , Margalida Antoni 
Published: July 2021

AbstractIn reintroduction projects, an analysis of dispersal, exploratory movements and territorial behavior of the species concerned offers valuable information on the adaptive management of threatened species and provides a basis for the management of future reintroductions. This is the case of the Iberian lynx (Lynx pardinus) an endemic and endangered species reintroduced in Extremadura (Spain) in 2014. We analysed spatial data from 32 individuals just after their reintroduction. Our findings show exploratory movements sufficient to colonise and connect population nuclei within a radius of about 50 km of the reintroduction area. No significant differences were found in the exploratory movements capacity or in any directionality of males and females. Our results showed an effect of sex on the sizes of the territories established, as well as an inverse relationship between them and the time elapsed since release. No effects of rabbit abundance and lynx density on the size of territories are occurring during the early stages of reintroduction. On average, the territories of reintroduced individuals were less stable than those previously described in natural populations. Findings indicate that the reintroduced population has successfully been established but it takes more than 5 years to stabilize the territories in the area. Exploratory movements of reintroduced lynx can be large and in any direction, even when there is still a lot of high quality habitat available, which should be taken into account when reintroducing species, especially terrestrial carnivores.
Efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction in Taiwan
Authors: Lee Chih-Kuo , Wang Tzung-Dau , Juang Hsiao-Ting , Chang Shu-Chen , Pan Heng-Yu , Lin Donna Shu-Han , Chang Chee-Jen 
Published: July 2021

AbstractThe clinical efficacy of ticagrelor versus clopidogrel has not been replicated in East Asian populations. The pronounced bleeding risk with ticagrelor was of concern given the increased bleeding tendency in Asian populations. This study evaluated efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI) in the entire Taiwan. We used the Taiwan National Health Insurance Research Database to identify 6203 patients aged ≥ 20 years with NSTEMI hospitalization and prescription of dual antiplatelets at discharge between January 2014 and December 2014. Cohorts of ticagrelor and clopidogrel were matched 1:1 based on propensity score matching to balance baseline covariates. The primary composite efficacy endpoints included death from any cause, non-fatal myocardial infarction, and non-fatal stroke. The secondary efficacy endpoints were the individual components. The primary safety endpoint was major bleeding requiring hospitalization. The incidence of primary efficacy endpoint was 20.3% in the ticagrelor users and 20.7% in the clopidogrel users (adjusted HR 0.94; 95% CI 0.73–1.22), with the median (interquartile range, IQR) follow-up period of 5.2 (2.3–8.5) months. The incidence of primary safety endpoint was 2.3% in the ticagrelor users and 3.2% in the clopidogrel users (adjusted HR 0.67; 95% CI 0.33–1.35). Regarding the secondary efficacy endpoint, patients treated with ticagrelor had significantly lower incidence of stroke (adjusted HR 0.44; 95% CI 0.21–0.94; p = 0.033). In this nationwide Taiwanese cohort of NSTEMI, treatment with ticagrelor after discharge, as compared to clopidogrel, had similar rates of ischemic composite events and major bleeding. Nevertheless, the median follow-up time was only 5.2 months, and the reduced stroke events with ticagrelor compared to clopidogrel needs further verification.
Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells
Authors: Sato Mai , Inohaya Asako , Yasuda Eriko , Mogami Haruta , Chigusa Yoshitsugu , Kawasaki Kaoru , Kawamura Yosuke , Ueda Yusuke , Takai Hiroshi , Mandai Masaki , Kondoh Eiji 
Published: July 2021

AbstractPlacental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology.
The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice
Authors: Yu Xuhua , Cai Tiantian , Fan Long , Liang Ziyao , Du Qiuling , Wang Qi , Yang Zifeng , Vlahos Ross , Wu Lei , Lin Lin 
Published: July 2021

Abstract
Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking have been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit antiviral effects. Therefore, the aim of the present study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of proinflammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1β. The results demonstrated that JPYFII formulation exerted an antiviral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.
Glycoursodeoxycholic acid ameliorates diet-induced metabolic disorders with inhibiting endoplasmic reticulum stress
Authors: Cheng Lele , Chen Tao , Guo Manyun , Liu Peining , Qiao Xiangrui , Wei Yuanyuan , She Jianqing , Li Bolin , Xi Wen , Zhou Juan , Yuan Zuyi , Wu Yue , Liu Junhui 
Published: July 2021

Abstract
Recent studies reveal that bile acid metabolite composition and its metabolism are changed in metabolic disorders, such as obesity, type 2 diabetes and metabolic associated fatty liver disease (MAFLD), yet its role and the mechanism remain largely unknown. In the present study, metabolomic analysis of 163 serum and stool samples of our metabolic disease cohort was performed, and we identified glycoursodeoxycholic acid (GUDCA), glycine-conjugated bile acid produced from intestinal bacteria, was decreased in both serum and stool samples from patients with hyperglycemia. RNA-sequencing and quantitative PCR results indicated that GUDCA alleviated endoplasmic reticulum (ER) stress in livers of high fat diet (HFD)-fed mice without alteration of liver metabolism. In vitro, GUDCA reduced palmitic acid induced-ER stress and -apoptosis, as well as stabilized calcium homeostasis. In vivo, GUDCA exerted effects on amelioration of HFD-induced insulin resistance and hepatic steatosis. In parallel, ER stress and apoptosis were decreased in GUDCA-treated mice as compared with vehicle-treated mice in liver. These findings demonstrate that reduced GUDCA is an indicator of hyperglycemia. Supplementation of GUDCA could be an option for the treatment of diet-induced metabolic disorders, including insulin resistance and hepatic steatosis, with inhibiting ER stress.