bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of perinatal and maintained calorie restriction to mitochondrial level of oxidative stress in rat liver
Authors: Albarrán‐Bravo Sacnité , Pérez‐Gallardo Rocío V. , Clemente‐Guerrero Mónica , Manzo‐Ávalos Salvador , Saavedra‐Molina Alfredo 
Published: June 2021

Calorie restriction (CR) is known to extend the lifespan of a number of organisms including yeast, worms, flies, rodents and perhaps non‐human primates. The mechanisms through which occurs have been unclear. CR during gestation led to growth retardation at birth. If CR was prolonged throughout lactation, adult body weight was permanently reduced. There is also evidence that the intrauterine environment of the fetus may be of greater importance in the etiology of chronic diseases in adult fetus.The aim of this project is to determine the effect of a perinatal and maintained calorie restriction regimen in oxidative stress in rat liver mitochondria. Offsprings of one month of age showed a decreased in body weight of 48% in female and 56% in male rats. Levels of NO• in CR rats increased 180% in females and 282% in male rats compared to controls. Lipoperoxidation showed an increase of 211% in female and 116% in male rats under CR regimen against controls. Female and male rats of five months of age weighed 35% and 50%, respectively, less than controls. The determination of NO• shows a diminution of 56% in female and 36% in male rats under calorie restriction versus controls. The same can be seen in determination of lipoperoxidation with a diminution of a 54% in male rats but, in contrast, an increased in lipoperoxidation levels in female rats of 97% were observed versus controls. Our initial conclusion is that oxidative and nitrosative stresses are affected in offsprings of one month and in five month‐old. Supported by Fondos Mixtos CONACYT‐ Gob. Edo. de Michoacán (64277, 64308), COECYT and CIC‐UMSNH (2.16) grants.
Arachidonate distribution in resting and proliferating primary human T cells
Authors: Robichaud Philippe Pierre , Boulay Katherine , Poirier Samuel , Surette Marc E 
Published: June 2021

Arachidonate‐phospholipid remodelling is characterised by the transfer of arachidonate (AA) between cellular phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species. It has been suggested that AA‐phospholipid remodelling may control cellular AA distribution and availability.In this study, the cellular distribution of AA was measured in resting and in anti‐CD3+IL‐2 ‐stimulated primary human T cells. In pulse‐chase experiments a very rapid redistribution of [3H]AA from PC to PE was measured in stimulated proliferating cells compared to resting cells. This increased remodelling was accompanied by a marked shift in the mass distribution of AA into 1‐alkyl‐ and 1‐alk‐1‐enyl‐linked PE species in stimulated cells. Minor differences in AA distribution were measured in cells arrested in different phases of the cell cycle (G1/S, G2/M and S), with the most marked changes observed when the cells transitioned from G0 into the cell cycle. The re‐distribution of AA in proliferating T cells was reversed when the stimulus was removed and the cells ceased to proliferate. Previous studies linked the expression of group IVC phospholipase A­2 with a redistribution of AA into PE species suggesting a role for this enzyme in remodelling. However, remodelling activity was not modified in HEK293 cells overexpressing this enzyme, suggesting that a different isozyme is likely involved. Microarray experiments are now underway with the aim of identifying which enzymes are possibly involved in the remodelling of arachidonate in cycling human T cells. (Supported by the Canadian Institutes of Health Research and the Canada Research Chairs Program).
Critical role for nucleostemin in protein synthesis and muscle cell differentiation
Authors: Romanova Liudmila , Hirai Hiroyuki , Asakura Atsushi , Kikyo Nobuaki 
Published: June 2021

Nucleostemin (NS) is a nucleolar protein that was shown to be primarily expressed in proliferating cells and essential for proliferation but the precise functions of NS remained unclear. Here, we reveal a significant role for NS as an integrated component of ribosome biogenesis, particularly pre‐rRNA processing. The supporting data demonstrated physical interactions of NS with other processing‐related proteins, nucleolar retention of these proteins by NS, and inhibition of pre‐rRNA processing and protein synthesis in NS‐depleted cells. We also showed that unlike in other cell lineages, NS was not downregulated in differentiated skeletal muscle cells, which maintain highly active protein synthesis after exit from the cell cycle. Moreover, progress of muscle differentiation could be modulated by NS in a dose‐dependent manner. These results underscore a fundamental involvement of NS in cell proliferation and differentiation through its contribution to ribosome biogenesis and protein synthesis.This work was supported by Muscular Dystrophy Association, Korea Institute of Science and Technology, Nash Foundation and the NIH.
Leukocyte‐associated immunoglobulin‐like receptor (LAIR)‐2 is a soluble competitor of the collagen/LAIR‐1 inhibitory immune interaction
Authors: Meyaard Linde , van den Berg Maaike , de Ruiter Talitha , Raynal Nicholas , van Roon Joel , Lenting Peter , Jin Boquan , Lebbink Robert Jan 
Published: June 2021

Leukocyte‐associated Ig‐like receptor (LAIR)‐1 is a collagen‐receptor that inhibits immune cell function upon collagen binding (Lebbink et al, J Exp Med, 2006). Next to LAIR‐1, the human genome encodes LAIR‐2, a putative soluble homologue. We now show that the LAIR‐2 gene is broadly transcribed in human peripheral blood mononuclear cells, mirroring the expression profile of LAIR‐1. LAIR‐2 protein is expressed as a soluble receptor exhibiting high affinity for various collagen molecules to which it binds in a hydroxyproline‐dependent manner. In vitro stimulation of peripheral blood mononuclear cells induces secretion of LAIR‐2. Interestingly, high amounts of LAIR‐2 are detected in urine of pregnant women, indicating that the soluble receptor is indeed produced in vivo and can be cleared from the body via urine. Furthermore, LAIR‐2 levels are increased in synovial fluid of patients with rheumatoid arthritis as compared to osteoarthritis patients. We hypothesize that soluble LAIR‐2 may function as a natural competitor for LAIR‐1, thereby regulating its inhibitory potential. Indeed, LAIR‐2 prevents binding of human LAIR‐1 to collagens and LAIR‐1 crosslinking in vitro, revealing a novel mechanism of immune regulation by a soluble LAIR receptor regulating the inhibitory potential of the membrane‐bound LAIR‐1 via competition for ligands.Supported by the Netherlands Organization for Scientific Research (NWO)
Immunostimulatory activities of CMB, the water extract of Cordyceps militaris fruit bodies, in primary macrophages
Authors: Kim Kyungjae , Shin Seulmee , Kwon Jeunghak , Lee Sungwon , Kong Hyunseok , Lee Chongkil 
Published: June 2021

Cordyceps militaris has been used in traditional folk medicine to treat numerous diseases and reported to have antitumor and immunomodulatory activities in vivo and in vitro. The pharmacological and biochemical mechanisms of CMB on macrophages have not been clearly elucidated. We examined whether CMB induces the production of pro‐inflammatory cytokines and the expression of co‐stimulatory molecules. CMB increased the production of nitric oxide (NO) and pro‐inflammatory cytokines such as Interferon‐1 beta (IL‐1β), Interferon‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α) and prostaglandin E2 (PGE2) dose‐dependently. The change of gene expression level by CMB treatment was analyzed by using RT‐PCR, and the associated mRNA expression was increased same as cytokine production. Western blot analysis showed the augmentation of cytokine related protein on CMB treatment, and the expression of co‐stimulatory molecules such as ICAM‐1, B7‐1, B7‐2 also was enhanced with the increment of CMB concentration.These results provide the clues for understanding the macrophage activation mechanism by CMB in innate and adaptive immunity, and suggest that CMB could be useful immunomodulatory agent for treating immunological diseases.
TRAF3 inhibits signaling by Toll‐like receptors in B lymphocytes
Authors: Xie Ping , Brown Lindsey , Stunz Laura L. , Bishop Gail A. 
Published: June 2021

TRAF3, a cytoplasmic adaptor protein, binds directly to a number of receptors of the tumor necrosis factor receptor (TNF‐R) superfamily. To elucidate the physiological functions of TRAF3 in B lymphocytes, we recently generated B cell‐specific TRAF3‐deficient mice, and reported that TRAF3 is a critical regulator of peripheral B cell homeostasis. In light of the evidence that TRAF3 is required for type I interferon production induced by Toll‐like receptors (TLRs) in myeloid cells, the present study further investigated whether and how TRAF3 regulates signaling by TLRs in B lymphocytes. Interestingly, we found that B cell responses to agonists for TLR3, 4, 7/8 and 9, including surface molecule upregulation, cytokine production, and Ig isotype switching, were markedly enhanced by TRAF3 deficiency. Our findings indicate that in contrast to myeloid cells, TRAF3 inhibits TLR signaling in B lymphocytes, and suggest that TRAF3 may play important roles in modulating humoral immunity in response to pathogen infections.This study is supported by a grant from the American Heart Association (PX), NIH grants AI28847, AI49993, CA099997, and a VA Career Award (GAB).
T lymphocytes specific for vascular smooth muscle cells in a murine model of vasculitis
Authors: Baiu Dana Carina , Hart Michael N. 
Published: June 2021

We developed an inducible murine model of vasculitis. In this model, transfer of T cells to syngeneic recipients, after in vitro sensitization by co‐culture with syngeneic vascular cells, results in lymphocytic and granulomatous‐like systemic vasculitis. T cells are pathogenic in the absence of antibodies, because the vasculitis model has been successfully replicated in mice deficient in B cells (JgH‐J). We applied a limited proteomic approach combining iterative subcellular fractionation and antigen presentation to identify potential antigenic targets in vascular tissue that may contribute to T cell‐mediated inflammation. Activation of pathogenic T cells was evaluated by flow cytometry detection of early and late‐activation surface markers, intracellular cytokines and cell proliferation. Proteins from fractions enriched in endoplasmic reticulum / Golgi vesicles induced activation of CD4 T cells previously sensitized by live vascular smooth muscle cells. The data suggest that, in this mouse model, T cells specific for vascular smooth muscle autoantigens, possibly located in the endoplasmic reticulum / Golgi membrane fractions, are pathogenic for vasculitis.NIH grant R01HL48658
Th17 Differentiation by Dendritic Cells is Dependent on IL‐13
Authors: Baldeviano Geral Christian , Barin Jobert G. , Kimura Miho , Rose Noel R. , Cihakova Daniela 
Published: June 2021

Interleukin‐17 (IL‐17) drives the pathogenesis of a number of autoimmune disease models, including experimental autoimmune myocarditis (EAM). We have previously found that IL‐13 deficient (IL‐13 KO) mice developed severe EAM. To assess whether IL‐17 modulates the pathogenic response in heartss of IL‐13 KO mice, we determined the levels of IL‐17. Interestingly, IL‐17 was significantly decreased in spleen, heart (R&D Systems ELISA), and draining lymph nodes (by RT‐PCR) of IL‐13 KO mice at day 21 of EAM. Naïve IL‐13 deficient CD4+ T cells differentiated into Th‐17 cells and CD4+ FOXP 3+ T regulatory cells similar to naïve WT BALB/c T cells. However, bone marrow derived dendritic cells (BMDCs) from IL‐13KO mice were deficient in driving OVA323–339‐specific Th‐17 differentiation from naïve DO11.10 CD4+ T cells. This defect was partially restored when the BMDCs were cultured in the presence of recombinant IL‐13. IL‐13 deficient BMDCs expressed less MHCII, CD80, CD86 and CD40 upon maturation with LPS, b‐glucan curdlan, or antiCD40 mAb. Furthermore, IL‐13 deficient BMDCs produced less proinflammatory cytokines IL‐6 and TNFalpha after maturation with LPS. Thus, IL‐13 is required for DC maturation and cytokine production, which limits its ability to induce Th17. In summary, a decrease of IL‐17 in hearts of IL‐13 KO mice during EAM represents a general defect of IL‐13 KO DCs in inducing Th‐17.Supported by 2R01 HL67290
Expansion of CD4+ regulatory T cells by BMDC in the absence of exogenous IL‐2 and TGFβ is determined by the strength of the TCR signal
Authors: Turner Michael Stuart , Morel Penelope A 
Published: June 2021

Our group has previously reported that onset of Type 1 diabetes could be delayed in NOD mice by administration of BMDC grown with GM‐CSF & IL‐4 (G4DC) and enriched for high‐exfpression of MHC II and co‐stimulatory molecules, whereas DC grown with only GM‐CSF (GMDC) were not therapeutically effective. By studying the interaction of tolerogenic G4DC with CD4+ T cells from BDC2.5 TCR Tg mice, we have found that G4DC can induce proliferation of both Foxp3+ (Treg) and Foxp3− (Th) CD4+ T cells, in the absence of exogenous IL‐2 or TGFβ.In these experiments CFSE‐labeled BDC2.5 CD4+ T cells were cultured with G4DC, pulsed with increasing doses of high‐ and low‐affinity peptide mimetopes. The presence of Treg in proliferating in and non‐proliferating T cells was assessed after 7 days by ICC for FoxP3. We observed a significant expansion of FoxP3+ Treg when low doses of specific peptides were used, whereas high peptide doses induced expansion of effector T cells. This phenomenon is not unique to self‐reactive T cells since similar results were obtained in the OVA‐specific DO11.10 TCR Tg system.Interestingly, G4DC also induced expansion of Tregs from nontransgenic NOD CD4+ T cells, whether or not the DCs were peptide‐pulsed, suggesting that G4DC from NOD mice may present low levels of endogenous self‐antigen.These data suggest that therapeutic G4DC function, in part, by inducing Treg expansion and that, in the absence of exogenous TGF‐β, the strength of the TCR signal is critical for Treg expansion/induction.Funded by the American Diabetes Association (PM).
Optimizing anti‐tumor immunity: Mechanisms and reversion of systemic iNKT defects in murine prostate cancer
Authors: Nowak Michael , Ilyinski Petr , Arredouani M. Simo , Sanda Martin , Balk Stephen P , Exley Mark A 
Published: June 2021

Breaking tolerance to self‐antigens represents a promising treatment approach, especially for cancers of noncritical organs. Invariant natural killer T cells(iNKT) recognize glycolipids presented on CD1 molecules by dendritic and related cells and regulate immune reactions.In numerous model studies, α‐GalCer administration activates iNKT to inhibit pre‐existing and spontaneous tumors as well as metastases.Importantly, in multiples types of model and human cancers numerical iNKT defects have been found. Moreover, decreased iNKT numbers were accompanied by reversible functional iNKT defects such as decreased IFN‐γ production in advanced prostate cancer and progressive multiple myeloma, resulting in a deleterious Th2 cytokine response of iNKT in such patients.We analyzed numerical and functional NKT cell defects in the murine TRAMP prostate cancer (PCa) model. In this model, probasin‐directed expression of SV40 T antigen drives the sequential development of dysplasia (prostatic intraepithelial dysplasia, PIN), locally invasive tumors, and metastatic disease resembling features of human PCa.Tumor‐bearing 20 wks. old TRAMP mice revealed systemic decreases in iNKT numbers. Furthermore, iNKT from TRAMP mice exhibited upon α‐GalCer stimulation a clear Th2 bias both in vitro and in vivo compared to WT littermates. Since we have shown that the latter iNKT defects are reversible in vitro, we are investigating reversing these defects in vivo.We are analyzing the mechanisms which contribute to the observed Th2 bias to optimize iNKT anti‐tumor effector function towards Th1 type in tumor‐bearing mice. Focus is examining impact on tumor progression in TRAMP mice upon adoptive transfere of in vitro expanded iNKT, as in our concurrent iNKT clinical trial for cancer.
Involvement of regulatory T cells and Th17 cells in ovarian endometriosis and ovarian epithelial tumors
Authors: Vlad Anda Mioara , Budiu Raluca , Thaller Julia , Edwards Robert P. , Finn Olivera J. 
Published: June 2021

Endometriosis is a chronic inflammatory disorder defined as abnormal growth of endometrial tissue at ectopic sites, most often on the ovary. Women with endometriosis are at higher risk of developing ovarian cancer. We recently generated a mouse model for ovarian endometriosis, using the previously established LSL‐KrasG12D mice, which we crossed with MUC1 transgenic mice. Following intra‐bursal administration of Cre‐encoding adenovirus, the MUC1Kras mice develop de novo, endometriosis‐like lesions. Interestingly, these mice show an increased percentage of FoxP3+ regulatory T cells in their spleens and para‐aortic lymph nodes but fewer Th17.We also investigated the pattern of FoxP3, IL‐17, TGF‐b, IL‐1 and IL‐6 mRNA expression in human ovarian endometriosis and ovarian cancer using qRT‐PCR. Our results from a total of 23 patients (normal donors, physiological ovarian cysts, endometriosis, ovarian tumors with paired ascites) show that FoxP3 was detected in the ascites of all tested patients and in the majority of tumor specimens but also in 6 out of 9 of patients with endometriosis, confirming our results in mice. IL‐17 was also up‐regulated in 55% of endometriosis cases and it was highly up‐regulated in ovarian cysts. Further studies on the immune imbalance in premalignancy (endometriosis) and ovarian cancer in mice and humans are in progress. Research support from the Continuing Medical Research Fund (AMV).
High dietary energy intake during pregnancy increases net gestational weight gain in overweight and obese women
Authors: Rahn Maike , Strawderman Myla S , Olson Christine M 
Published: June 2021

Limited information is available about the relationship between dietary energy intake and gestational weight gain. Three hundred and twenty‐six women from rural New York participated in a prospective observational study. Dietary intake (Willet FFQ), physical activity level and SES were assessed once with mail‐in questionnaires between the 1st and 3rd trimester; maternal gestational weight gain (GWG), maternal height and infant birth weight were collected with chart reviews. Women with underweight BMI, inadequate GWG or inconsistent reporting of dietary intake were excluded. Energy balance (EB) was created by subtracting estimated total energy expenditure from dietary energy intake (EI); EB was categorized into negative, adequate and positive balance groups (cutoffs −300 and 300 kcal). Women were on average 28 years old, and 43% had a high BMI of >26 kg/m2. Mean GWG was 33.7±9.5 lbs, and 54% experienced excessive GWG. Mean net GWG was 25.6±9.4 lbs. Reported mean EI was 2480±756 kcal, mean EB was −102±817 kcal. EB and EI were highly correlated (r=0.9, p=0.03). EI tertiles were associated with net GWG in the overall group (trend p<0.05), but not in the BMI subgroups. Energy balance was associated with GWG and net GWG (trend p<0.05) in the overall sample; however, when separating normal and high BMI women, only the group with BMI >26 kg/m2 showed a significant increase (trend p<0.05) of GWG and net GWG with EB. High BMI women had a mean GWG of 29, 32, and 33 lbs for the negative, adequate and positive balance groups, respectively. Mean net GWG was 20, 24, and 25 lbs, respectively. In conclusion, increased dietary energy intake results in greater net GWG, but only in high BMI women.This research was supported by the NIH postdoctoral grant R21 DK69448.
Examining the dietary amino acid characteristics of patients on ketogenic therapy
Authors: Nathoo Sunina , Borum Peggy R. 
Published: June 2021

Ketogenic Therapy (KT) is a high fat, adequate protein, low carbohydrate diet shown to reduce seizures in patients with intractable epilepsy. While KT has been used for decades, the building blocks of the dietary components such as amino acids have not been examined. The usual diet prescription ratio of grams of fat to grams of carbohydrate plus grams of protein assumes that the all protein is the same and has the same effect on the therapy as carbohydrate. To evaluate dietary protein characteristics in patients on KT, data were collected via weekly 24 hour dietary recalls taken from 14 patients on KT. The Minnesota Database (NDS) was used to analyze these recalls. Some of the dietary protein characteristics are listed in the table below.The characteristics of dietary amino acids vary among pediatric patients on ketogenic therapy for seizures. Characteristics such as the ratio of ketogenic amino acids to gluconeogenic amino acids may impact the therapy and these potential impacts need to be evaluated.
Evaluation of metabolism‐boosting beverages on resting energy expenditure
Authors: Coleman Christopher D. , Rampolla Joni , Kiel Jessica , Davis Lisa M. 
Published: June 2021

Objective: To evaluate the effect of thermogenic meal replacement beverages (TMRB) containing 90mg ECGC and 100mg of caffeine on resting energy expenditure (REE).Subjects: 30 adults (19 women, 11 men) were stratified into 3 groups: lean (n=10, BMI 21.5 ± 2.1); overweight/obese (OW) (n=10, BMI 29.8 ± 2.7); or weight maintainers (WM) (n=10, BMI 28.8 ± 4.0, maintained wt loss of ≥5% body wt for ≥3 mos).Methods: Following an overnight fast, baseline measures of ht, wt, WC, bp, pulse, and REE via indirect calorimetry were performed. REE was repeated at 30, 60, 90, and 120 min after consuming a TMRB. Appetite was assessed via visual analogue scale at baseline, 30 min and 120 min after consuming the TMRB.Results: Overall, mean REE increased 24.0 ± 10.1% for the 2‐hr period following the consumption of a TMRB. Mean 24‐hr REE was increased 5.9 ± 2.5% overall (p=0.000), 5.7 ± 3.1% among lean subjects (p=0.0002), 5.3 ± 1.4% among OW subjects (p=0.000), and 6.8 ± 2.7% among WM (p=0.0007). There was a trend toward increased fat oxidation (p=0.116). Appetite was significantly reduced 30 min after consuming the TMRB (p=0.0002), but not at 120 min.Conclusion: Our findings suggest 3 potential benefits of TMRB in weight control: increases in resting energy expenditure, increases in fat oxidation, and decreases in appetite. Decreases in energy in and increases in energy out should translate into improved weight loss and weight maintenance.
Fruit, Vegetable consumption and Body Weight
Authors: Pereira Paula Cardoso , Vicente Ana Filipa 
Published: June 2021

Low fruit and vegetable consumption has been associated with other erratic food habits which lead to overweight and obesity. In the present study, we compare weight and body mass index (BMI) with vegetable soup, vegetables as side dish and fruit consumption.A total of 25 men had their weight and height measured, we calculated their BMI and obtained vegetable and fruit consumption by food diary and average intake recall.This data showed that only 10% were in their normal weight but even obese and overweighed men had healthy habits about vegetable and fruit consumption. The vast majority reported that it was an habit to consume vegetable soup in 1 to 2 meals but vegetables in both main meals (lunch and dinner). Fruit intake reported accomplished even more WHO recommendations (1 – 3 servings/day).Several secondary aspects can influence these men's food choices, mainly soup and vegetable availability where they eat. This results may show that even overweighed and obese can have some healthy food habits.