bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of peripheral NGF attenuates neuropathic pain induced by chronic constriction injury through the TAK1-MAPK/NF-κB signaling pathways
Authors: Dai Wen-Ling , Yan Bing , Bao Yi-Ni , Fan Ji-Fa , Liu Ji-Hua 
Published: April 2020

AbstractBackgroundAnti-nerve growth factor (NGF) monoclonal antibodies (anti-NGF mAbs) have been reported to significantly attenuate pain, but the mechanism involved has not been fully elucidated, and the serious adverse events associated with mAbs seriously limit their clinical use. This study further investigated the mechanism by which peripheral NGF is involved in neuropathic pain and found safe, natural compounds that target NGF to attenuate neuropathic pain.MethodsNociception was assessed by the Von Frey hair and Hargreaves’ methods. Western-blotting, qPCR and immunofluorescence were used to detect the cell signaling pathway. RAW264.7 macrophages and RSC96 Schwann cells were cultured for in vitro evaluation.ResultsIntraplantar administration of anti-NGF mAbs suppressed the expression of phosphorylated transforming growth factor-β-activated kinase 1 (TAK1) in the dorsal root ganglion (DRG) and sciatic nerve. Intraplantar administration of a TAK1 inhibitor attenuated CCI-induced neuropathic pain and suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPKs) in the DRG and sciatic nerve. Perisciatic nerve administration oflevo-corydalmine (l-CDL) on the operated side obviously attenuated CCI-induced neuropathic pain and suppressed the expression of mNGF and proNGF. In addition,l-CDL-induced antinociception was reversed by intraplantar administration of NGF. Further results indicated thatl-CDL-induced suppression of phosphorylated TAK1, MAPKs, and p65 and expression of the proinflammatory cytokines TNF-α and IL-1β in the DRG and sciatic nerve were all abolished by NGF. In addition, in vitro experiments indicated thatl-CDL suppressed the secretion of NGF and proNGF in RAW264.7 macrophages and RSC96 Schwann cells, which was abolished by AP-1 and CREB agonists, respectively.ConclusionsThis study showed NGF inhibition suppressed TAK1 in the periphery to attenuate CCI-induced neuropathic pain through inhibition of downstream MAPK and p65 signaling. The natural compoundl-CDL inhibited NGF secretion by macrophages and Schwann cells and downstream TAK1-MAPK/NF-κB signaling in the periphery to attenuate CCI-induced neuropathic pain.Graphical abstractProposed mechanisms underlying the effect ofl-CDL in periphery of CCI rats. In CCI rats, macropahages and Schwann cells could secret NGF to act on the receptors in the periphery to activate TAK1-MAPK/NF-κB axis and promote the release of proinflammatory cytokines, including TNF-α and IL-1β to promote neuropathic pain.l-CDL decreased the secretion of NGF through inhibiting AP-1 and CREB respectively in RAW264.7 and RSC96 Schwann cells to attenuate CCI-induced neuropathic pain by inhibiting the TAK1-p38 MAPK/NF-κB signaling pathway.
High-mobility group box 1 protein antagonizes the immunosuppressive capacity and therapeutic effect of mesenchymal stem cells in acute kidney injury
Authors: Wang Shuo , Cai Songjie , Zhang Weitao , Liu Xigao , Li Yan , Zhang Chao , Zeng Yigang , Xu Ming , Rong Ruiming , Yang Tianshu , Shi Benkang , Chandraker Anil , Yang Cheng , Zhu Tongyu 
Published: April 2020

Abstract
Background
Kidney ischemia reperfusion injury (IRI) is a common cause of acute kidney injury and an unavoidable consequence of kidney transplantation and still lacks specific therapeutics. Recently, mesenchymal stem cell (MSC) has been emerging as a promising cell-based therapy for IRI in the context of transplantation. MSC negatively regulates the secretion of pro-inflammatory as well as the activation of immune cells during IRI through its unique immunosuppressive property.

Methods
We employed mice kidney IRI model and MSC cell line to monitor the IRI related checkpoints. siRNAs were utilized to knock down the potential key factors for mechanistic analysis. Statistical analysis was performed by using one-way ANOVA with Tukey’s post hoc procedure by SPSS.

Results
The expression of high-mobility group box 1 protein (HMGB1) is increased in the acute phase as well as the recovery stage of IRI. Importantly, the HMGB1 upregulation is correlated with the injury severity. HMGB1 diminishes the MSC induced immunosuppressive capacity in the presence of pro-inflammatory cytokines in vitro. Toll like receptor 4 (TLR4)-mediated inducible nitric oxide synthase (iNOS) inhibition contributes to the negative effect of HMGB1 on MSCs. HMGB1-TLR4 signaling inhibition augments the therapeutic efficacy of MSCs in mice renal IRI model.

Conclusions
These findings demonstrate that HMGB1 plays a crucial role in shaping the immunoregulatory property of MSCs within the microenvironments, providing novel insights into the crosstalk between MSCs and microenvironment components, suggesting HMGB1 signals as a promising target to improve MSC-based therapy.
Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice
Authors: Fan Jun-Juan , Gao Bo , Song Ao-Qi , Zhu Ya-Jing , Zhou Jun , Li Wei-Zu , Yin Yan-Yan , Wu Wen-Ning 
Published: April 2020

AbstractBackgroundDry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch.MethodsDry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion.ResultsAEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively.ConclusionsSpinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.
Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy
Authors: Allegretti Matteo , Cottone Giuliano , Carboni Fabio , Cotroneo Ettore , Casini Beatrice , Giordani Elena , Amoreo Carla Azzurra , Buglioni Simonetta , Diodoro Maria , Pescarmona Edoardo , Zazza Settimio , Federici Orietta , Zeuli Massimo , Conti Laura , Cigliana Giovanni , Fiorentino Francesco , Valle Mario , Giacomini Patrizio , Spinella Francesca 
Published: April 2020

Abstract
Background
Liquid biopsy (LB) in early-stage, non-metastatic colorectal cancer (CRC) must be sensitive enough to detect extremely low circulating tumor DNA (ctDNA) levels. This challenge has been seldom and non-systematically investigated.

Methods
Next generation sequencing (NGS) and digital PCR (dPCR) were combined to test tumor DNAs (tDNAs) and paired ctDNAs collected at surgery from 39 patients, 12 of whom were also monitored during the immediate post-surgery follow up. Patients treated for metastatic disease (n = 14) were included as controls.

Results
NGS and dPCR concordantly (100% agreement) called at least one single nucleotide variant (SNV) in 34 tDNAs, estimated differences in allelic frequencies being negligible (±1.4%). However, despite dPCR testing, SNVs were only detectable in 15/34 (44.1%) ctDNAs from patients at surgery, as opposed to 14/14 (100%) metastatic patients. This was likely due to striking differences (average 10 times, up to 500) in ctDNA levels between groups. NGS revealed blood-only SNVs, suggesting spatial heterogeneity since pre-surgery disease stages, and raising the combined NGS/dPCR sensitivity to 58.8%. ctDNA levels at surgery correlated with neither tumor size, stage, grade, or nodal status, nor with variant abundance in paired tDNA. LB sensitivity reached 63.6% when ctDNA was combined with CEA. Finally, persistence and absence of ctDNA on the first conventional (month 3) post-surgery follow-up were associated with fast relapse and a disease-free status in 3 and 7 patients, respectively.

Conclusions
A simple clinical NGS/dPCR/CEA combination effectively addresses the LB challenge in a fraction of non-metastatic CRC patients.
NOTCH2 variant D1853H is mutated in two non-syndromic premature ovarian insufficiency patients from a Chinese pedigree
Authors: Li Lin , Feng Fan , Zhao Minying , Li Tengyan , Yue Wentao , Ma Xu , Wang Binbin , Yin Chenghong 
Published: April 2020

Abstract
Background
Premature ovarian insufficiency (POI) is a severe disorder of female infertility, characterized by 4–6 months of amenorrhea before the age of 40 years, with elevated follicle stimulating hormone (FSH) levels (> 25 IU/L). Although several genes have been reported to contribute to the genetic basis of POI, the molecular mechanism of POI remains unclear.

Methods
Whole-exome sequencing (WES) was performed. Sanger sequencing was carried out to validate the variant in the proband and her mother. In silico algorithms were used to analyze the mutational effect of the variant. Protein 3D structural modeling was used for predicting mutated protein structures. Vector construction and plasmids transfection were performed, and subsequently RNA-sequencing (RNA-seq) was carried out in each group to dissect the differentially expressed genes in wild-type (WT) and D1853H NOTCH2 mutant expressing groups. Gene Ontology analysis was also used to analyze the enriched biological processes or pathways among the differentially expressed genes.

Results
We report two non-syndromic POI patients from a Chinese pedigree. The FSH level of the proband (the daughter) was 46 IU/L at the age of 22. Her menarche was at the age of 12, but she was amenorrhea at the age of 20. By WES, a rare heterozygous variant (c.5557G > C;p.D1853H) in the NOTCH2 gene was identified. In silico analysis suggested that p.D1853H was a pathogenic allele. Protein 3D structural modeling suggested that D1853H may enhance or weaken the electrostatic surface potential. By molecular analysis, we found that cells expressing the D1853H NOTCH2 mutant had similar effect in activating the NOTCH signaling pathway downstream target genes. However, 106 protein-coding genes were differentially expressed between D1853H expressing cells and WT NOTCH2 expressing cells, and these genes were enriched for collagen degradation, NCAM1 interactions and HDACs deacetylate histones, revealing a unknown underlying mechanism of the pathology that leads to POI.

Conclusions
We conclude that the rare heterozygous variant in NOTCH2 may be associated with POI. This finding provides researchers and clinicians with a better understanding of the etiology, molecular mechanism and genetic consulting of POI.
scATAC-pro: a comprehensive workbench for single-cell chromatin accessibility sequencing data
Authors: Yu Wenbao , Uzun Yasin , Zhu Qin , Chen Changya , Tan Kai 
Published: April 2020

AbstractSingle-cell chromatin accessibility sequencing has become a powerful technology for understanding epigenetic heterogeneity of complex tissues. However, there is a lack of open-source software for comprehensive processing, analysis, and visualization of such data generated using all existing experimental protocols. Here, we present scATAC-pro for quality assessment, analysis, and visualization of single-cell chromatin accessibility sequencing data. scATAC-pro computes a range of quality control metrics for several key steps of experimental protocols, with a flexible choice of methods. It generates summary reports for both quality assessment and downstream analysis. scATAC-pro is available athttps://github.com/tanlabcode/scATAC-pro.
High-solids enzymatic hydrolysis of ball-milled corn stover with reduced slurry viscosity and improved sugar yields
Authors: Lu Minsheng , Li Junbao , Han Lujia , Xiao Weihua 
Published: April 2020

AbstractBackgroundHigh-solids enzymatic hydrolysis has attracted increasing attentions for the production of bioethanol from lignocellulosic biomass with its advantages of high product concentration, water saving, and low energy and capital costs. However, the increase of solids content would worsen the rheological properties, resulting in heat/mass transfer limitation and higher mixing energy. To address these issues, ball milling was applied to corn stover prior to enzymatic hydrolysis, and the rheological behaviors and digestibility of ball-milled corn stover under high-solids loading were investigated.ResultsBall milling significantly modified the physicochemical properties of corn stover. The apparent viscosity of slurries at 30% solid loading decreased by a factor of 500 after milling for 60 min, and the yield stress was less than 10 Pa. The dramatic decrease of viscosity and yield stress enabled the hydrolysis process to be conducted in shake flask, and remained good mixing. Meanwhile, the estimated energy consumption for mixing during saccharification decreased by 400-fold compared to the untreated one. The resultant hydrolysate using 10 FPU g−1solids was determined to contain 130.5 g L−1fermentable sugar, and no fermentation inhibitors were detected.ConclusionsThe proposed ball milling pretreatment improved rheological behavior and sugar yield of high-solids corn stover slurry. Ball milling enables high-solids slurry to maintain low viscosity and yield stress while obtaining a non-toxic high-concentration fermentable syrup, which is undoubtedly of great significance for inter-unit processing, mixing and downstream process. In addition, the energy input for ball milling could be balanced by the reduced mixing energy. Our study indicates ball milling a promising pretreatment process for industrial bioethanol production.
Amblyomma hebraeum is the predominant tick species on goats in the Mnisi Community Area of Mpumalanga Province South Africa and is co-infected with Ehrlichia ruminantium and Rickettsia africae
Authors: Jongejan Frans , Berger Laura , Busser Suzanne , Deetman Iris , Jochems Manon , Leenders Tiffany , de Sitter Barry , van der Steen Francine , Wentzel Jeanette , Stoltsz Hein 
Published: April 2020

AbstractBackgroundIn sub-Saharan Africa,Amblyommaticks are vectors of heartwater disease in domestic ruminants, caused by the rickettsial pathogenEhrlichia ruminantium. Immature tick stages often bite humans, whereby they act as vectors of tick-bite fever caused byRickettsia africae.Moreover,Amblyommaticks cause damage to livestock due to their feeding behaviour. In South Africa, we studied the abundance ofAmblyomma hebraeumticks on goats of emerging farmers in Mpumalanga Province. A selected number ofA. hebraeumnymphs and adult ticks was tested for co-infection withE. ruminantiumandR. africae.MethodsA total of 630 indigenous goats, belonging to farmers in the Mnisi Community area, were examined for ticks in 2013 and 2014. All ticks were identified, and a selected number was tested by PCR with reverse line blot hybridisation.ResultsIn total, 13,132 ticks were collected from goats distributed over 17 different households.Amblyomma hebraeumwas the predominant species, followed byR. microplus.Rhipicephalus appendiculatus,R. simusandR. zambeziensiswere also identified.Amblyomma hebraeumwas present throughout the year, with peak activity of adults in summer (November) and nymphs in winter (July). The ratio between adults and nymphs ranged from 1:2.7 in summer to 1:55.1 in winter. The mean prevalence of infection forE. ruminantiumby PCR/RLB in adult ticks was 17.4% (31/178), whereas 15.7% (28/178) were infected withR. africae. In pooled nymphs, 28.4% were infected withE. ruminantiumand 38.8% carriedR. africaeinfection. Co-infections ofE. ruminantiumandR. africaein adult and pooled nymphal ticks were 3.9% (7/178) and 10% (14.9), respectively. Lameness of goats due to predilection of ticks for the interdigital space of their feet was observed in 89% of the households.ConclusionsGoats act as important alternative hosts for cattle ticks, which underscored the necessity to include goats in control programs. It is suggested to use acaricide-impregnated leg-bands as a sustainable method to kill ticks and prevent lameness in goats. The challenge of goats by considerable numbers ofE. ruminantium-infected ticks is a major obstacle for upgrading the indigenous goat breeds. Humans may be at risk to contract tick-bite fever in this area.
Survey of Dirofilaria immitis antigen and antibodies to Leishmania infantum and Toxoplasma gondii in cats from Madeira Island, Portugal
Authors: Neves Michelle , Lopes Ana Patrícia , Martins Carolina , Fino Raquel , Paixão Cláudia , Damil Liliana , Lima Clara , Alho Ana Margarida , Schallig Henk D. F. H. , Dubey Jitender P. , Cardoso Luís 
Published: April 2020

AbstractBackgroundDirofilaria immitis,Leishmania infantumandToxoplasma gondiiare zoonotic parasites which can affect domestic cats. Considering the lack of published data from the local feline population, this study aimed to assess infection with or exposure to these pathogens in cats from Madeira Island, Portugal.MethodsOne hundred and forty-one domestic cats (77 males and 64 females; median age: 2 years) were sampled at a veterinary medical centre in Funchal, from September 2018 to January 2019. Serum samples were tested forD. immitisantigen, with an enzyme-linked immunosorbent assay kit, and for antibodies toLeishmaniaspp. or toT. gondii, with the direct agglutination test and the modified agglutination test, respectively.ResultsFive cats (3.5%; 95% confidence interval, CI: 1.2–8.1) were positive toD. immitis; no cats were seropositive toLeishmaniaspp. (0%; 95% CI: 0–2.6%); and 43 cats (30.5%; 95% CI: 23.0–38.8%) were seropositive toT. gondii. Prevalence of theD. immitisantigen was significantly different between cats that received ectoparasiticides and those which did not (0vs12.2%;P = 0.009). Prevalence of antibodies toT. gondiiwas significantly different between juvenile and adult cats (12.8vs38.0%;P = 0.007). There were two cats concurrently positive toD. immitisandT. gondii, but no statistical association between these two dependent variables was found (P = 0.641).ConclusionsTo our knowledge, this is the first report of the presence of parasitesD. immitisandT. gondiiin the feline population of Madeira Island. Knowledge on the epidemiological situation of these and other zoonotic pathogens should raise awareness, both at the veterinary medical and public health levels, and contribute to promoting prevention and control.
Successful chemotherapy management of disseminated intravascular coagulation presenting with metastatic clear cell renal carcinoma: a case report and review of the literature
Authors: Le Trinh Huy , Nguyen Vuong Thi , Mai Ngan Kim , Tran Bach Trung , Pham Quynh Nga 
Published: April 2020

Abstract
Background
Disseminated intravascular coagulation is a critical complication of advanced clear cell renal cell carcinoma, despite the rarity of the occurrence of disseminated intravascular coagulation in such tumors. The diagnosis of cancer-related disseminated intravascular coagulation is mostly based on clinical bleeding and laboratory test; available data suggest that treating the primary cancer also treats the disseminated intravascular coagulation. Among three reported cases of renal cell carcinoma-related disseminated intravascular coagulation in the literature, this is the first patient whose disseminated intravascular coagulation was successfully treated, in particular, with chemotherapy without any anti-disseminated intravascular coagulation therapies.

Case presentation
This case is a 66-year-old Vietnamese man who presented disseminated intravascular coagulation 2 weeks after his admission for severe back pain. At admission, his initial laboratory work-up revealed only a mild thrombocytopenia with a platelet count of 93 × 109/L (normal range, 150–450 × 109/L) without clinical bleeding. His past medical history and family history were unremarkable. An open-biopsy was performed and the definitive diagnosis was bone metastatic clear cell renal cell carcinoma based on immunohistochemistry. Two weeks after admission, the diagnosis of disseminated intravascular coagulation was confirmed according to the International Society on Thrombosis and Haemostasis. Immediately, he was treated with a paclitaxel plus carboplatin regimen and disseminated intravascular coagulation completely disappeared after one cycle of systemic chemotherapy. Until recently, 11 months subsequent to the diagnosis of disseminated intravascular coagulation, he had been being undergoing maintenance therapy for metastatic clear cell renal cell carcinoma.

Conclusions
First, an early detection of overt disseminated intravascular coagulation is essential, although disseminated intravascular coagulation in cancer presents as a chronic or even subclinical process with unique thrombocytopenia. Second, making a decision of systemic chemotherapy without delay at the time of disseminated intravascular coagulation diagnosis is the key to successful cancer-related disseminated intravascular coagulation treatment.
Identification of genes involved in xylose metabolism of Meyerozyma guilliermondii and their genetic engineering for increased xylitol production
Authors: Atzmüller Denise , Ullmann Nadine , Zwirzitz Alexander 
Published: April 2020

AbstractMeyerozyma guilliermondii, a non-conventional yeast that naturally assimilates xylose, is considered as a candidate for biotechnological production of the sugar alternative xylitol. Because the genes of the xylose metabolism were yet unknown, all efforts published so far to increase the xylitol yield of this yeast are limited to fermentation optimization. Hence, this study aimed to genetically engineer this organism for the first time with the objective to increase xylitol production. Therefore, the previously uncharacterized genes of M. guilliermondii ATCC 6260 encoding for xylose reductase (XR) and xylitol dehydrogenase (XDH) were identified by pathway investigations and sequence similarity analysis. Cloning and overexpression of the putative XR as well as knockout of the putative XDH genes generated strains with about threefold increased xylitol yield. Strains that combined both genetic modifications displayed fivefold increase in overall xylitol yield. Enzymatic activity assays with lysates of XR overexpressing and XDH knockout strains underlined the presumed functions of the respective genes. Furthermore, growth evaluation of the engineered strains on xylose as sole carbon source provides insights into xylose metabolism and its utilization for cell growth.