bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in miRNA‐mediated regulation of thrombospin‐2 in developing placenta of the BPH/5 mouse model of pre‐eclampsia (PE)
Authors: Zhou Yi , Guruju Mallikarjuna R , Woods Ashley K , Sharma Ram V , Davisson Robin L 
Published: June 2021

We have recently shown severe fetoplacental abnormalities in the BPH/5 model of PE. Given the importance of miRNAs in regulating gene expression during embryonic development, we hypothesized that changes in miRNA expression in developing placenta of BPH/5 may be involved in fetoplacental defects observed in this model. We employed miRNA microarrays to analyze whole genome miRNA expression in feto‐placental units from BPH/5 (e10.5) over three classes of phenotype severity. Ninety‐four miRNAs were differentially expressed in BPH/5 feto‐placental units compared to C57 controls (fold change >1.5, p<0.05, n=3). miR‐467b and miR‐136 were down‐regulated and validated by real time RT‐PCR (Table 1). miRNA target prediction identified thrombospdin‐2 (Thbs‐2) as a target gene of miR‐467b and miR‐136. Western analysis showed a significant increase Thbs‐2 levels in all three classes of BPH/5 fetoplacental units vs C57 (Table 1). These results suggest that increased expression of Thbs‐2 in BPH/5 placentas due to decreased miRNA‐mediated post‐transcriptional repression may be inhibiting angiogenesis, ultimately leading to fetoplacental abnormalities observed in this model of PE.Table 1. miR‐467b and miR‐136 miRNA and Thrombospodin‐2 protein expression in different classes of BPH/5 feto‐placental unit compared to C57*<0.05 vs. C57
The Utility Value of Olfactory Ensheathing Cells (OEC) and Olfactory Nerve Fibroblasts (ONF) in Treating Spinal Cord Injury
Authors: Kanakasabapathy Indirani , Tharion George 
Published: June 2021

IntroductionCurrently many stem cell sources are being tried to treat patients with spinal cord injury. However, the utility value of these cells is under debate. Here, we report the outcome of our study in treating spinal cord injury using olfactory ensheathing cells (OEC) and olfactory nerve fibroblasts (ONF) transplantation in adult albino rat.MethodOlfactory ensheathing cells and olfactory nerve fibroblasts were isolated from rat olfactory mucosa and cultured under appropriate culture conditions. Four weeks after crush injury of spinal cord, OEC and ONF were injected into the lesion site. The outcome, in terms of limb movements was assessed using BBB scale and EMG study. The animal was sacrificed and the cord segments of interest were processed for histological examination.ResultNine months after the transplantation, the functional outcome was scored as '17' on BBB scale and the EMG study revealed generation of motor impulses in muscles of paralyzed limbs. Histological examination showed newly formed neural tissue and reduction of post‐traumatic degenerative changes.ConclusionOur finding confirms that OEC and ONF have the potential to improve neurologic disfunction and supports the utility of these cells in cell therapy treatment for CNS lesion.
Intragastric infusion of arginine stimulated greater liver protein synthesis compared to IV infusion in TPN‐fed Yucatan miniature piglets
Authors: Dinesh Chandani , Dodge M Elaine , Baldwin Mark P , Bertolo Robert F , Brunton Janet A 
Published: June 2021

Total parenteral nutrition (TPN) induced gut atrophy reduces de novo synthesis of intestinal arginine (Arg) in neonates which may limit Arg availability. Our objective was to assess the effect of route of Arg intake on tissue protein synthesis in TPN‐fed piglets with gut atrophy. Piglets (14‐17 d) were fed TPN (1.0 g Arg/kg/d) until study d 4, then switched to Arg‐free TPN and randomized to receive a continuous intragastric infusion (2 mL/kg/hr) of either IG Low Arg (0.6 g/kg/d) or IG High Arg (1.6 g/kg/d). A 3rd group was switched to high Arg TPN (1.6 g/kg/d) (IV High Arg). A group of sow‐fed (SF) littermates was also included. On d 7, piglets received an IV flooding dose of 3H‐phenylalanine to measure protein synthesis (Ks, %/d). Liver Ks was greater in IG High Arg compared to IV High Arg. Mucosal Ks was highest in SF animals, with no differences in the TPN‐fed groups. Table values are mean (SD), N=3‐6 per tissue and group. Different superscripts by row, p<0.05 (ANOVA)Provision of high dietary Arg alone into the gut did not appear to enhance mucosal protein synthesis. Muscle protein synthesis was also not different, but was highly variable. IG delivery of Arg promoted liver protein synthesis compared to IV feeding; the mechanism is likely not related to Arg availability as there was no difference in liver free Arg. (CIHR)
Dilutional fluorescent method to measure glomerular albumin reflection coefficient (dσAlb) in vitro
Authors: Schreck Carlos Manuel Nicolas , Williams Jan Michael , Sharma Mukut , Roman Richard J 
Published: June 2021

This study describes a new high throughput method (7‐15 glomeruli/experiment, 3 experiments/hour) to measure dσAlb. Adult SD rats received FITC‐Dextran 250 ( 75 mg/Kg. iv) and 5 minutes later the kidneys were harvested and glomeruli isolated using a sieving technique in 6% BSA. They were studied in a small volume (50 μl) fast exchange chamber on an inverted fluorescent microscope equipped with InCytIm 1 imaging system using a 10X (0.3 NA) objective. Changes in the fluorescent signal in the glomerular capillaries due to water movement in response to an imposed oncotic gradient were used to determine dóAlb. Changing the bath from 6 to 5, 4, 3, 2 % albumin produced a linear 12, 26, 37 and 52% fall in the concentration of FITC‐Dextran250 in the glomerulus ( r2=0.95). Administration of protamine sulfate ( 2 mg/ml) or TGF‐β1 (10 ng/ml) to increase the glomerular permeabilty to albumin, decreased dσAlb from 1 to 0.6 and from 1 to 0.67 , respectively. Fluorescence increased 10 % in glomeruli treated with protamine and exposed to an isotonic solution of Dextran 250 but not in control glomeruli. These results validate this high throughput method to measure changes in dσAlb in response to drug administration and between normal animals and those with proteinuria and renal disease.NIH grants: HL 36279 and HL 29587
Tranilast protects from renal injury in streptozotocin‐induced diabetic Dahl salt sensitive rats
Authors: Hosoya Takuma , Mori Takefumi , Ohsaki Yusuke , Yoneki Yoshimi , Nakamichi Takashi , Nagasawa Tasuku , Sato Hiroshi , Ito Sadayoshi 
Published: June 2021

The present study was designed to investigate the role of tranilast (TL), which inhibits TGF‐beta, in the renal injury and oxidative stress of streptozotocin (STZ)‐induced diabetic Dahl salt sensitive (Dahl S) rats and compared to the insulin (INS) treatment.Dahl S rats were administered with STZ (65mg/kg)(STZ), STZ with TL (400mg/kg/day) (STZ+TL), STZ with INS (10U/kg/day) (STZ+INS), or STZ with INS and TL (STZ+INS+TL). Urinary albumin and TBARS excretion was analyzed as a marker of renal injury and oxidative stress, respectively.Blood glucose level of STZ and STZ+TL groups (572.83±37.3, 639.71±27.5 mg/dl) were significantly higher than those of STZ+INS and STZ+INS+TL groups (330.83±61.39, 221.14±83.41 mg/dl). Systolic blood pressure was increased in all groups, but did not have difference between groups. Urinary albumin excretion was significantly decreased in STZ+TL group (43.6±6.3 mg/day) and STZ+INS group (41.7±7.1 mg/day) compared to STZ group (76.5±6.9 mg/day), and further decrease in STZ+INS+TL group (24.6±3.1 mg/day). Reduction in urinary TBARS excretion was observed only in STZ+INS group compared to STZ group.These results indicate that tranilast protects from renal injury independent of blood pressure, blood glucose level and oxidative stress in diabetic Dahl S rats.
Synbiotic modulation of cytokine secretion in ulcerative colitis colonic biopsies
Authors: Urdaneta Elena , Alfaro Maria , Jauregui Patricia , Zozaya Jose Manuel , Arin Antxon , Santidrian Santiago , Marzo Florencio 
Published: June 2021

Ulcerative colitis (UC) consists of an aberrant local immune response to components of the bacterial microflora. There is also evidence that mucosal immune cells actively interact with non‐immune cells to promote tissue damage, and that cytokines are essential mediators of this cross‐talk. Functional foods, with beneficial effects for human health, such as a synbiotic, composed of Lactobacillus casei (Lc) and Bifidobacterium bifidum (Bb) (108 cfu/mL), and sphingomyelin (0.05%), could modulate this inflammatory disease.The aim of this study was to investigate pro and anti‐inflammatory cytokine production in colonic biopsies from UC patients and healthy volunteers examining this synbiotic effect.Patients were asked to give written consent to take part in this investigation. These studies were approved by the Hospital de Navarra Ethics Committee. Production of proinflammatory Th1 cytokines (TNF‐alpha, IFN‐gamma, IL‐1B, IL‐6 and IL‐8) and anti‐inflammatory Th2 cytokines (IL‐10 and IL‐13)) was analyzed in mucosal biopsies of patients with UC (n=10) and control subjects (n=10) by flow cytometry using Cell Quest software (Becton Dickinson).The incubation of synbiotic reduced significantly (P< 0.01) the secretion of IL‐6, IL‐1beta and IL‐8 in biopsies of UC patients. The anti‐inflammatory Th2 cytokine levels were not affected either by UC disease or by synbiotic treatment.These findings suggest a new immunomodulatory function of this symbiotic compound and further suggests that these bacteria may be useful in the treatment of UC.This work has been funded by Ortiz de Landazuri of Navarra Government and Ministry of Education & Science (AGL2006‐10296).
Pathogenic and commensal Escherichia coli decrease ion secretion in human intestinal epithelial cells
Authors: Ohland Christina , MacNaughton Wallace K 
Published: June 2021

E. coli enteric bacteria consist of commensal and pathogenic strains, including enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) E. coli. The genetically similar mouse pathogen Citrobacter rodentium decreases ion secretion in vivo. Our aim was to investigate how E. coli strains affect secretion in vitro.Exposure of T84 cell monolayers to EPEC or EHEC for 4 hr significantly decreased the response to the cAMP‐dependent secretagogue, forskolin, without altering Ca2+‐dependent secretion as measured in Ussing chambers. EPEC mutants deficient in flagellin, bundle forming pili, Type III secretion, Tir or intimin invoked similar hyposecretory responses, indicating that these factors are not involved. Pre‐treatment with the apoptosis inhibitor Z‐VAD did not alter this effect. Lab strain (HB101) and human commensal (C1, C28/2, F18) E. coli decreased secretion to a similar extent. Heat‐killed or paraformaldehyde‐fixed EPEC, sterile culture medium or E. coli lipopolysaccharides did not cause hyposecretion. Adenylate cyclase activity is not altered by EPEC, as a cAMP assay showed no change in baseline or stimulated levels. EPEC does not alter protein levels of CFTR or NKCC1 as shown by Western blot.We conclude that pathogenic and commensal E. coli decrease cAMP‐dependent ion secretion in vitro by an unknown bacterial factor, downstream of cAMP production. Funded by III Summit Foundation & CCFC.
Gastro‐protective Properties of Cobiprostone against Acid‐induced Mucosal Injury in Porcine Gastric Mucosa
Authors: NIGHOT MEGHALI PRASHANT , ROERIG BIRGIT , UENO RYUJI , MOESER ADAM J , BLIKSLAGER ANTHONY 
Published: June 2021

Activation of ClC‐2 Cl− channels is an important mechanism of intestinal mucosal barrier repair. Lubiprostone, a prostone known to activate epithelial ClC‐2 Cl− channels, has been shown to hasten repair of ischemic‐injured intestinal mucosa. The objective of the present study was to evaluate the gastro protective properties of the novel prostone, cobiprostone, in a porcine model of gastric acid injury. We hypothesized that cobiprostone would ameliorate acid injury associated with maintenance of tight junctions and activation of chloride channels. Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH=1.5). Transepithelial resistance and mucosal‐to‐serosal 3H‐mannitol flux was measured over a 90 minute period. Compared with control tissues, acid exposure decreased TER and increased 3H‐mannitol flux. Pretreatment of gastric mucosa with cobiprostone was protective against acid‐induced decreases in TER and abolished increases in flux .Histological damage were attenuated in cobiprostone treated gastric mucosa exposed to acid. Immunofluorescence and western analysis for occludin revealed enhanced localization of to the tight junction after treatment. Pretreatment with the ClC‐2 inhibitor ZnCl2, and the CFTR inhibitor DASU attenuated cobiprostone mediated mucosal protection, indicating a critical role for Cl− channels.The Research is funded by Sucampo Pharmaceuticals, Inc. Bethesda, MD
Cyclooxygenase 2 inhibition exacerbates AQP2 and pAQP2 downregulation independently of V2 receptor abundance in the postobstructive kidney
Authors: Jensen Anja M , Norregaard Rikke , Bae Eun Hui , Wang Guixian , Nielsen Søren , Kim Soo Wan , Frøkiær Jørgen 
Published: June 2021

The type 2 vasopressin receptor (V2R) and vasopressin‐regulated transport proteins is downregulated in postobstructive kidney. ANG II receptor (AT1R) blockade attenuates V2R, AQP2 and pAQP2 downregulation and partially reverses obstruction‐induced inhibition of cAMP generation. Furthermore, AT1R blockade attenuates cyclooxygenase 2 (COX2) induction and as COX2 inhibition attenuates AQP2 downregulation 3 days after release of bilateral ureteral obstruction (BUO) we speculated if the effects of AT1R blockade on V2R and the vasopressin‐regulated pathway are due to reduced prostaglandin E2 generation.Rats were subjected to 24h BUO followed by 48h release and treated with parecoxib, a specific COX2 inhibitor, or saline. Control rats were sham‐operated. Urine output, water intake, and solution free water clearance were comparable in parecoxib‐ and saline‐treated rats. Immunoblotting, revealed a significant decrease in AQP2 and pAQP2 abundance to 20% and 23% of sham levels in BUO+P rats compared to 40% and 55% of sham levels in saline‐treated BUO rats. V2R abundance decreased to less than 10% of sham in both BUO and BUO+P rats. Finally, vasopressin‐stimulated cAMP generation in inner medullary membrane fractions from BUO+P rats tended to be reduced compared to BUO rats.In conclusion, COX2 inhibition exacerbates AQP2 and pAQP2 downregulation 48h after release of 24 h BUO independently of V2R abundance
Oral Tolerance Reduces Eosinophil and Neutrophil Activation in a Cockroach Antigen Murine Model of Allergic Asthma.
Authors: Vaickus Louis J , Remick Daniel 
Published: June 2021

Our lab previously demonstrated that German cockroach allergens (CRA) induce allergic‐type airways inflammation in outbred (ICR:CD‐1) mice which closely resembles human allergic asthma. We sought to determine the efficacy of oral tolerization in alleviating asthmatic symptoms. Mice were given 8ug/day CRA by oral gavage for 4 days beginning with day ‐7, followed by intratracheal challenges with 4.75ug on day 0 and 2.4ug on days 14 and 21. Cytokines and cellular content were measured in the bronchoalveolar lavage fluid and cytokines and myeloperoxidase activity were measured in lung homogenate. Samples were collected 4 hours post final challenge and the results compared to PBS fed, CRA challenged mice. In the BAL, Eo2 and TNF were significantly reduced in tolerized mice while KC, IL‐17 and absolute Eos trended towards reduced in tolerized mice. In the lung homogenate, Eo1 and KC were significantly reduced in tolerized mice, while TNF, IL‐17 and myeloperoxidase activity trended towards reduced in tolerized mice. These results indicate that oral tolerance partially abrogates eosinophil infiltration into the lung space, as well as a decrease in parenchymal neutrophil infiltration/activation. These beneficial effects are probably mediated through a reduction in the levels of prominent cytokines associated with asthma induction and progression.Table 1: Cytokines and Cells in BAL measured in pg/mL. Cytokines and peroxidase activity in LH measured in pg/mL and absorbance versus blank resp. NM = not measured.
Renal cell carcinoma, part 1
Authors: Pullen Richard L. 
Published: June 2021

Abstract:
Renal cell carcinoma (RCC) encompasses a group of malignancies that originate in the epithelium of the renal cortex, most often in the upper pole of the kidney. This article, the first of a three-part series on RCC, addresses the incidence and epidemiology of RCC along with its genetic alterations, risk factors, histologic characteristics, and imaging characteristics.
Niclosamide inhibits SARS-CoV2 entry by blocking internalization through pH-dependent CLIC/GEEC endocytic pathway
Authors: Prabhakara Chaitra , Godbole Rashmi , Sil Parijat , Jahnavi Sowmya , van Zanten Thomas S , Sheth Dhruv , Subhash Neeraja , Chandra Anchal , Nuthakki Vijay Kumar , Puthiyapurayil Theja Parassini , Ahmed Riyaz , Najar Ashaq Hussain , Lingamallu Sai Manoz , Das Snigdhadev , Mahajan Bhagyashri , Vemula Praveen , Bharate Sandip B , Singh Parvinder Pal , Vishwakarma Ram , Guha Arjun , Sundaramurthy Varadharajan , Mayor Satyajit 
Published: June 2021

AbstractMany viruses utilize the host endo-lysosomal network to infect cells. Tracing the endocytic itinerary of SARS-CoV2 can provide insights into viral trafficking and aid in designing new therapeutic targets. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV2 is internalized via the clathrin and dynamin-independent, pH-dependent CLIC/GEEC (CG) endocytic pathway. Endosomal acidification inhibitors like BafilomycinA1 and NH4Cl, which inhibit the CG pathway, strongly block the uptake of RBD. Using transduction assays with SARS-CoV2 Spike-pseudovirus, we confirmed that these acidification inhibitors also impede viral infection. By contrast, Chloroquine neither affects RBD uptake nor extensively alters the endosomal pH, yet attenuates Spike-pseudovirus entry, indicating a pH-independent mechanism of intervention. We screened a subset of FDA-approved acidification inhibitors and found Niclosamide to be a potential SARS-CoV2 entry inhibitor. Niclosamide, thus, could provide broader applicability in subverting infection of similar category viruses entering host cells via this pH-dependent endocytic pathway.
Histone H3 lysine 27 acetylation profile undergoes two global shifts in undernourished children and suggests one-carbon metabolite insufficiency
Authors: Kupkova Kristyna , Shetty Savera J. , Haque Rashidul , Petri William A. , Auble David T. 
Published: June 2021

AbstractBackgroundStunting is a condition in which a child does not reach their full growth potential due to chronic undernutrition. It arises during the first two years of a child’s life and is associated with developmental deficiencies and life-long health problems. Current interventions provide some benefit, but new approaches to prevention and treatment grounded in a molecular understanding of stunting are needed. Epigenetic analyses are critical as they can provide insight into how signals from a poor environment lead to changes in cell function.ResultsHere we profiled histone H3 acetylation on lysine 27 (H3K27ac) in peripheral blood mononuclear cells (PBMCs) of 18-week-old and one-year-old children living in an urban slum in Dhaka, Bangladesh. We show that 18-week-old children destined to become stunted have elevated levels of H3K27ac overall, functional analysis of which indicates activation of the immune system and stress response pathways as a primary response to a poor environment with high pathogen load. Conversely, overt stunting at 1-year-of age is associated with globally reduced H3K27ac that is indicative of metabolic rewiring and downregulation of the immune system and DNA repair pathways that are likely secondary responses to chronic exposure to a poor environment with limited nutrients. The results from one-year-old children also point toward deficiency in one-carbon metabolism, which is further supported by integrative analysis with results from histone H3 trimethylation on lysine 4 (H3K4me3).ConclusionsThe epigenomes of stunted children undergo two global changes in H3K27ac within their first year of life, which are associated with probable initial hyperactive immune responses followed by reduced metabolic capacity. Limitation of one-carbon metabolites may play a key role in the development of stunting. Trial registration:ClinicalTrials.govNCT01375647. Registered 17 June 2011, retrospectively registered.
Mild Adverse Events of Sputnik V Vaccine Extracted from Russian Language Telegram Posts via BERT Deep Learning Model
Authors: Jarynowski Andrzej , Semenov Alexander , Kamiński Mikołaj , Belik Vitaly 
Published: June 2021

AbstractBackgroundThere is a limited amount of data on the COVID-19 vector vaccine Gam-COVID-Vac (Sputnik V) safety profile. Previous infodemiology studies showed that social media discourse could be analyzed to assess the most concerning adverse events (AE) caused by drugs.ObjectiveWe aimed to investigate mild AEs of Sputnik V based on a participatory trial conducted on Telegram in the Russian language. We compared AEs extracted from Telegram with other limited databases on Sputnik V and other COVID-19 vaccines. We explored symptom co-occurrence patterns and determined how counts of administered doses, age, gender, and sequence of shots could confound the reporting of AEs.Materials and MethodsWe collected a unique dataset consisting of 11,515 self-reported Sputnik V vaccine AEs posted on the Telegram group, and we utilized natural language processing methods to extract AEs. Specifically, we performed multi-label classifications using the deep neural language model BERT “DeepPavlov”, which we pre-trained on a Russian language corpus and applied to the Telegram messages. The resulting AUC score was 0.991. We chose symptom classes that represented the following AEs: fever, pain, chills, fatigue, nausea/vomiting, headache, insomnia, lymph node enlargement, erythema, pruritus, swelling, and diarrhea.ResultsThe results of the retrospective analysis showed that females reported more AEs than males (1.2-fold, P<.001). In addition, there were more AEs from the first dose than from the second dose (1.13-fold, P<.001), and the number of AEs decreased with age (β= .05 per year, P<.001). The results also showed that Sputnik V AEs were more similar to other vector vaccines (132 units) compared with mRNA ones (241 units) according to the average Euclidean distance between the vectors of AE frequencies. Elderly Telegram users reported significantly more (5.6-fold on average) systemic AEs than their peers, according to the results of the phase III clinical trials published inThe Lancet. However, the AEs reported in Telegram posts were consistent (Pearson correlation r=.94, P=.02) with those reported in the Argentinian post-marketing AE registry.ConclusionAfter receiving the Sputnik V vaccination, Telegram users complained about pain (47%), fever (47%), fatigue (34%), and headache (25%). The results showed that the AE profile of Sputnik V was comparable with other COVID-19 vaccines. Examining the sentinel properties of participatory trials (which is subject to self-reporting biases) could still provide meaningful information about pharmaceutics, especially if only a limited amount of information on AEs is provided by producers.