bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved fungal cell wall carbohydrates are targets of natural antibodies and direct adaptive antibody responses against Pneumocystis carinii
Authors: Rapaka Rekha R , Zheng Mingquan , Kolls Jay K
Published: June 2021

Fungal pathogens contain conserved cell wall carbohydrates that may be targets of multiple host defense pathways. We hypothesize that B cells produce Abs specific to fungal wall carbohydrates and that these enhance host resistance to the opportunistic fungus Pneumocystis carinii (PC). We find that SPF mice contain high serum titers of β‐glucan and chitin specific IgM, which are equally abundant in germ‐free mice, suggesting that these specificities are part of the natural Ab repertoire. Natural IgM secreting B cells specific for these carbohydrates predominate in the spleen, and we present data on the role of these Abs in the dynamics of innate host defense against PC. Upon murine PC challenge, we observe an adaptive B cell response to β‐glucan and chitin, consisting of a transient enhancement of specific IgM and a delayed, pronounced specific IgG response in the serum, as well as enrichment of IgG, IgA, and IgM against these epitopes within the lung mucosa. The pulmonary IgA response against these antigens is CD4+ T cell dependent while the IgG and IgM responses are not. Additionally, memory B cells specific for fungal carbohydrate antigens enrich in the spleen after PC challenge. Our data describe novel roles for PC carbohydrates as targets of innate and adaptive Ab responses and underscore the complexity of T cell dependence on the production of Ab targeting carbohydrates antigens. Support: NIH RO1HL061271, F30ESO1541
Characterizing effector cells at the host:parasite interface
Authors: Kreider Timothy , Boucher Jean‐Luc , Gause William C
Published: June 2021

BALB/c mice develop chronic infection upon exposure to the intestinal helminth Heligmosomoides polygyrus; the rapid clearance of subsequent re‐infection is a model for the Th2‐polarized memory response. Using immunofluorescence microscopy and laser microdissection‐assisted real‐time PCR, we examined the immune cell infiltrate surrounding the invading parasite at day 4 post‐infection, in order to identify potential effector cells mediating worm expulsion. Whereas infection in naïve mice resulted in a homogeneous Gr‐1high infiltrate, the response to infection in previously immunized mice was characterized by three CD11b+ populations with distinct patterns of Gr‐1 and F4/80 expression and located in specific regions surrounding the parasite. One of these populations stained positive for markers of alternatively activated macrophages (AAMΦ), and another population stained Gr‐1+/F4/80+, suggestive of inflammatory macrophages. Blockade of the Arginase‐1 pathway characteristic of AAMΦ resulted in abrogation of the protective memory response to H. polygyrus, as measured by worm and egg burdens 14 days post‐infection. Ongoing studies are examining the effects of selective depletion of specific Gr‐1 cell populations. These studies indicate the development of a distinct, localized, memory Th2 inflammatory response at the host:parasite interface shortly after infection, a subpopulation of which is required for worm expulsion.
T‐cell regulation of neutrophil trafficking during Staphylococcus aureus infections can regulate pathogenesis outcomes
Authors: McLoughlin Rachel Mary , Lee Jean C , Kasper Dennis L , Tzianabos Arthur O
Published: June 2021

Neutrophils are the first line of host‐defense in S. aureus infection and are critical in determining disease outcome. Evidence also suggests that S. aureus can survive inside neutrophils to exacerbate infection. We now demonstrate CXC chemokine‐induced internalization of S. aureus by neutrophils at the infection site using a murine model of surgical wound infection. To elucidate mechanisms controlling neutrophil recruitment to the infection site, we explore the novel concept that a sub set of neutrophil regulating T‐cells are activated during S. aureus infection and control the local neutrophil response. We demonstrate that S. aureus‐capsular polysaccharide ‐8 can activate T‐cell production of Interferon‐γ (IFN‐γ) in a MHC‐class II pathway dependant manner. We observe increased production of IFN‐γ locally during S. aureus wound infection, a process dependent upon αβTCR+ T‐cells. In addition IFN‐γ−/− mice demonstrate decreased CXC chemokine production and associated neutrophil recruitment to the infection site compared to wild‐type mice. This reduced neutrophil influx is associated with lower tissue bacterial burden, suggesting that a neutrophil rich environment potentiates pathogenesis due to the bacteria's ability to survive within the neutrophil. It is clear that neutrophil recruitment must be tightly controlled during wound infection and we identify IFN‐γ as a central regulator of this process.
Galectin‐3 regulates cytokine production and bacteria burden in macrophages during Listeria infection
Authors: Weng I‐Chun , Hsu Daniel K. , Liu Fu‐Tong
Published: June 2021

Galectin‐3 is a β‐galactoside‐binding animal lectin expressed in various immune cell types and has been implicated in immune and inflammatory responses during infectious disease processes. However, the mechanism of how galectin‐3 regulates macrophage's antibacterial function remains unclear. We proposed to elucidate the role of galectin‐3 in macrophage‐mediated inflammatory and innate immune responses by using bone marrow‐derived macrophages (BMM) from wild‐type (WT) and galectin‐3‐deficient (gal3−/−) mice for in vitro experiments, and a Listeria monocytogenes (LM)‐infected mouse model for in vivo experiments. The production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines as well as phagocytosis ability and intracellular bacteria number in LM‐infected WT and gal3−/− BMM were compared. Significantly lower amounts of IL‐12, IL‐1β, and IL‐6 were produced by LM‐infected gal3−/− BMM compared to WT BMM. No significant differences in ROS and NO production or phagocytosis of LM were observed. However, at 24 hr post‐infection, gal3−/− BMM contained dramatically lower number of intracellular bacteria than WT. These results suggest that galectin‐3 plays an important role in regulating cytokine production and intracellular bacteria load in macrophages during LM infection process.
MyD88 signaling is not essential for induction of antigen‐specific B cell responses but is indispensable for protection against Pneumonia infection following oral vaccination with attenuated Salmonella expressing PspA antigen
Authors: Park Sung‐Moo , Yang Jin‐Young , Uematsu Satoshi , Akira Shizuo , Curtiss Roy , Kweon Mi‐Na
Published: June 2021

Toll‐like receptors (TLRs) directly induce innate host defense responses, but the mechanisms of TLR‐mediated adaptive immunity remain subject to debate. In this study, we clarified the role of TLR‐mediated innate immunity for induction of adaptive immunity by oral vaccination with live recombinant attenuated Salmonella (S.) typhimurium vaccine (RASV) strain expressing Pneumonia surface protein A (PspA) antigen. Interestingly, oral vaccination with RASV expressing PspA resulted in identical levels of PspA‐specific IgG and IgA Ab responses in the serum and fecal extracts of MyD88−/− mice when compared with those of wild‐type C57BL/6 mice. In support of these results, similar numbers of PspA‐specific IgG and IgA Ab‐secreting cells were detected in the spleen and small and large intestines both of MyD88−/− mice and wild‐type mice. Moreover, Ag‐specific serum IgG and intestinal IgA Abs are normally induced in MyD88−/−TRIF−/− mice by oral immunization with attenuated Salmonella strain expressing PspA. Of most interest, MyD88 mediated signaling is crucial for efficient protection in both sepsis and lung pneumonia models. Taken together, these results suggest that innate immunity activated by MyD88 signals might not be necessary for antigen specific Ab induction but is critical for protection following oral vaccination with attenuated Salmonella expressing PspA.
MKP‐1 inhibits iNOS expression during the innate immune response to LPS
Authors: Liu Yusen , Zhao Qun , Wang Xianxi , Nelin Leif D.
Published: June 2021

Nitric oxide (NO) is a potent antimicrobial substance and a powerful vasodilator. Inducible NO synthase (iNOS) is responsible for the substantial NO production that occurs with microbial infection. Induction of iNOS in macrophages plays a critical role for the eradication of intracellular pathogens. Moreover, the excessive production of NO by iNOS has also been implicated in the pathogenesis of septic shock syndrome. Previously, we have demonstrated that mice deficient in mitogen‐activated protein kinase phosphatase (Mkp)‐1 exhibit exaggerated inflammatory responses and rapidly succumb to lipopolysaccharides (LPS). In response to LPS, Mkp‐1−/− mice produce greater amounts of inflammatory cytokines and NO than wild type mice, and exhibit severe hypotension. To understand the molecular basis for the increases in NO production, we studied the role of Mkp‐1 in the regulation of iNOS expression. We found that LPS challenge elicited a stronger iNOS induction in Mkp‐1 knockout mice than in wild type mice. Likewise, LPS treatment also resulted in greater iNOS expression in Mkp‐1−/− macrophages than in wild type cells. Both accelerated gene transcription and enhanced mRNA stability contribute to the increases in iNOS expression in LPS‐stimulated Mkp‐1−/− macrophages. We found that two transcription factors known to mediate iNOS induction, Stat1 and IRF1, were more potently activated by LPS in Mkp‐1−/− macrophages than in wild type cells, explaining the accelerated iNOS gene transcription in the Mkp‐1−/− cells. Our results suggest that augmentation of MKP‐1 expression may be a novel treatment for patients suffering from sepsis and septic shock.
Modifying the school environment by reducing portion size of lunch meal entrees
Authors: Chu Yen Li , Vickers Zata , Reicks Marla
Published: June 2021

Meal energy density can be decreased if children eat more fruits and vegetables and smaller portions of entrées. We examined whether children increased fruit and vegetable intake to compensate for reduced portion size of lunch entrées. We conducted a pilot study in a low‐income K‐8th grade school (mean = 330 students eating school lunch/d). Full portions of 5 entrées were served during 10 control days and a choice of full or half portions of the same entrées were served during 10 intervention days. Accompanying foods were held constant in each condition. Plate waste was measured to compare mean intake of entrées, fruits and vegetables/student/d by condition. Students (n=31) answered survey questions about taking half portions. Only 10% or fewer selected half portions when made available which was observed to vary with the popularity of the entrée and student age. No significant differences were observed by condition in entrée, fruit or vegetable consumption with the exception of apple intake which increased when half portions were offered. Consumption of all entrées was generally high in both conditions (78–90% of food taken) while fruit and vegetable intake was lower (64% of food taken). Survey responses indicated that selection of half portions of entrées would be based on liking, hunger and usual intake. In this study, making half portion size entrées available at school lunch was not likely to affect meal energy density.
The impact of a curriculum‐based intervention on dietary intakes and physical activity among primary school children
Authors: Nichols Selby , Francis Marlon , Dalrymple Nequesha
Published: June 2021

In this study, we evaluated the impact of a curriculum‐based nutrition intervention programme on dietary behaviours among 10‐year old children attending primary school. Half of the schools meeting the inclusion criteria were assigned to the intervention group (IVG) while the other half was assigned to the non‐intervention group (NIVG). The intervention consisted of a short curriculum based on six one‐hour modules based on the Bloom Taxonomy for mastery conducted over a one month. Modules consisted of theoretical and practical activities that fostered learning of the key concepts such as food groups, nutrients and their functions and portion sizes and participation in physical activity. A pre‐tested standardized questionnaire was used to collect demographic and behavioural items at baseline and four months later. The study was conducted from October 1, 2006 to March 31, 2007. A total of 572 students (248 in the IVG and 224 in the NIVG) participated fully in the study. 18% of the participants had only one measurement (either at baseline or post‐intervention) and were not a part of the statistical analyses. Our results show that the intervention resulted in highly significant decrease in the average consumption of fried foods, high sugar/high fat snack and sodas and significant increases in the in the consumption of fruits and participation in moderate‐to‐high intensity physical activity in school in the short‐term.
The Current Status of Adult Overweight and Obesity in Urban and Suburban Areas of Liaoning, China
Authors: Li Suijing , Li Hui
Published: June 2021

To describe status of adult overweight and obesity in urban and suburb areas of Liaoning, we used data from China Health and Nutrition Survey, including 8119 adults: 4745 in urban areas and 3374 in suburb areas. Overweight, obesity, and abdominal obesity were defined by WHO recommended cutoff points of BMI and waist circumference. The prevalence of overweight was 30.6%, obesity 6.1% and abdominal obesity 43.0%. They increased with age in urban areas, but prevalence of overweight peaked at 40~49 yrs and obesity at 50~59 yrs in suburb areas. Prevalence of obesity and abdominal obesity varied among occupations, with highest in retired people and lowest in inexperienced labor workers, but not among different education levels and difference income groups. In conclusion, obesity distribution in Liaoning province differs from other provinces in China. Whether the causes are unique or just a function of higher income and greater economic development remains to be studied.
Feeding acutely increases MyoD1 and decreases myostatin mRNA in human skeletal muscle
Authors: Atherton Philip , Smith Gordon , Villareal Dennis , Rankin Debbie , Mittendorfer Bettina , Rennie Michael
Published: June 2021

Feeding a mixed meal doubles muscle protein synthesis (MPS) within 90 min, an effect sufficiently rapid to be mostly due to changes in anabolic signalling. We examined the possibility that feeding may also acutely modulate transcriptional activity of genes controlling muscle mass, viz, MyoD1 and myostatin.

We studied the effect of intermittent small meals (Ensure®, to provide 70 mg protein·kg Fat free mass −1·h−1) in older men and women who were matched for age (65–80 y) and BMI. MPS was measured by incorporation of D3‐leucine into mixed muscle protein (13 men, 16 women). RT‐PCR was used to analyse changes in the expression in quadriceps muscle (7 men, 7 women) of the hypertrophy‐associated transcription factor, MyoD1 and myostatin, a negative regulator of muscle mass, with 28s mRNA used as a reference gene.

The rate of postabsorptive MPS was ∼25% less in men than in women (P=0.02). At 2.5 h after beginning feeding, MPS increased by 30% (P<0.01) but only in men. Expression of mRNA for myostatin and MyoD1 were identical in men and women in the postabsorptive state, but feeding decreased expression of myostatin mRNA by 63±9% (P<0.05) and increased that of myoD by 83±5% (P<0.01).

Thus, feeding acutely modulates the expression of genes likely to promote a milieu conducive to potential increases in muscle mass but these changes seem not to match the lack of an acute response of MPS to feeding in older women.
Markers of iron status in highly active and sedentary young women
Authors: St. Thomas Megan M. , Woolf Kathleen , Hahn Nicole L. , Vaughan Linda A. , Hinton Pamela S. , Carlson Amanda
Published: June 2021

Study examined iron status in highly active (n=28; 20±2 y; ≥ 12 h purposeful physical activity [PPA] per week) and sedentary women (n=28; 24±3 y; ≤ 2 h PPA per week). Subjects completed a 7‐day weighed food record and blood draw [hemoglobin, hematocrit, C‐reactive protein, serum iron, % transferrin saturation, total iron binding capacity (TIBC), ferritin, transferrin receptor, transferrin receptor index]. Independent t‐tests compared mean values between groups. Reported intakes of energy (p<0.01), protein (p<0.01), iron (p<0.01), and non‐heme iron (p<0.01) were higher in active versus sedentary women. Higher mean transferrin receptor concentration (p<0.01) and transferrin receptor index (p<0.01) were found in active versus sedentary women. No significant differences were found between groups for other blood markers. Serum ferritin concentrations indicated iron depletion in 21% of active and 17% of sedentary women. Yet, 50% of active and 17% of sedentary participants were iron depleted as evidenced by the transferrin receptor index. Elevated serum transferrin receptor concentrations were observed in 14% of active and 3% of sedentary women. Although active women reported greater intake of iron, they had higher mean transferrin receptor and higher transferrin receptor index than sedentary women. Assessment of iron status in active women may require measures not commonly used in routine assessments.
The quantitation of ferritin in the seeds of staple crops: ELISA method development
Authors: Reddy Manju B. , Lukac Rebecca , Maneesha Aluru
Published: June 2021

Biofortification, breeding of crops rich in bioavailable micronutrients, is a low‐cost sustainable strategy for combating iron deficiency anemia (IDA), a most common nutritional deficiency. Plant ferritin is believed to provide highly bioavailable iron, however a method to measure ferritin in seeds is currently lacking. The objective of this study was to develop a simple, reliable assay to quantitate the ferritin in several staple crops. A highly immunogenic 22 amino acid common sequence was identified among the ferritin sequences from beans, wheat, maize and rice to produce both anti‐ferritin polyclonal and monoclonal antibodies. A rapid method for the crude extraction of ferritin from the seeds was developed. Both antibodies shown cross reactivity with ferritin from all seeds tested; however the degree of reactivity was found to be dependent on the type or the amount of total protein extracted from each seed. Using our developed indirect ELISA assay with the polyclonal antibody and recombinant pea ferritin standard, ferritin content was found to be 10.2±1.0, 4.38±0.9, 1.2±0.3, 0.38±0.1, and 0.04±0.01 μg/g in red beans, white beans, wheat, maize, and brown rice, respectively. This simple and reliable assay will facilitate the rapid screening of large numbers of seeds and can be used by plant breeders to breed ferritin‐rich crops for providing highly bioavailable iron foods to combat IDA.
Ventral midbrain vs. striatal iron infusion to correct altered in vivo dopaminergic signaling in ID rats
Authors: Bianco Laura Elizabeth , Rundle Sarah E , Ghramm Lindsay H , Beard John L
Published: June 2021

Iron deficiency (ID) results in altered monoamine functioning in vivo including decreased DA transporter (DAT) and D2 receptor densities, decreased intracellular DA, increased extracellular DA and altered communication between D2 and DAT. We attempted to remediate DA functioning in the striatum by rescuing iron status in the cell bodies (Ventral Midbrain‐VMB) or the terminal fields (Striatum‐ST) by iron infusion. Using in vivo microdialysis and no net flux we found that infusion of 26 pmols iron into the ST resulted in no change in striatal extraction fraction or D2R – DAT communication in either CN or ID. However, infusion of iron into the VMB resulted in decreased Ed as well as remediation of D2R‐DAT in ID rats. Although local increases in iron could not be detected by AA, transferrin receptor levels were decreased in the ST after iron infusion indicating iron was delivered to the target areas. Additionally, ELISA measurements found that striatal intracellular DA, extracellular DA, and TH levels were also returned to normal levels after VMB but not ST infusion in ID rats. These data indicate that appropriate iron status in the VMB is required for proper striatal dopaminergic functioning.
Phytase supplementation increases food efficiency ratios, performance activity and body composition in rats fed a low zinc diet
Authors: Scrimgeour Angus , Marchitelli Louis , Whicker Jered , Young Andrew J.
Published: June 2021

Phytic acid forms insoluble complexes with nutritionally essential minerals, including Zn. Addition of microbial phytase to low Zn diets improves Zn status and bone strength. The present study aimed to observe effects of phytase supplementation on food efficiency ratios (FER), body composition and activity in rats fed a high phytic acid, low Zn diet. Rats (n=72) were fed moderately Zn‐deficient (5ppm) diets either with (ZnLO+P) or without (ZnLO) 1,500U phytase/kg, or a Zn‐adequate (30ppm, ZnAD) diet for 9‐weeks, and were divided into voluntary exercise (EX) or sedentary (SED) groups, in a 3x2 design. Both phytase‐ and Zn‐supplementation increased the FER (P<0.01 compared to ZnLO). The ZnLO+P and ZnAD rats ran 56–75 km more distance than ZnLO rats (ns), with the ZnLO+P rats running more km/week (P<0.05) than the ZnLO rats by week 6. In vivo DXA analyses indicated significant phytase (P<0.01) and activity (P<0.02) effects on bone area (BA), but these effects were independent of each other. Zn‐supplementation of ZnLO diets increased BA, BMC and BMD, irrespective of activity. Voluntary running rats exhibit decreased BA and BMC, regardless of diet. Body fat (%) was reduced and lean body mass (%) was increased in EX rats, but neither was influenced by Zn‐ or phytase‐supplementation. This data suggest that if dietary Zn is limiting, supplemental phytase may have beneficial effects on FER, performance activity and body composition.
Gestational zinc deficiency leads to differential modulation of mitogen activated kinases in fetal brain
Authors: Keenan Alison Haller , Mackenzie Gerardo G , Aimo Lucila , Oteiza Patricia I
Published: June 2021

We previously showed that in neuroblastoma IMR‐32 cells, decreased zinc availability alters the modulation of the mitogen activated kinases (MAPKs) ERK1/2, p38 and JNK in association with decreased cell proliferation and increased apoptosis. We have now investigated the effects of feeding diets containing adequate (25 μg Zn/g, C) or marginal zinc (10 μg/g, MZD) concentrations throughout gestation on the modulation of MAPKs and the downstream activation of transcription factor AP‐1 in E19 rat fetal brain. Food intake, pregnancy and fetal outcome were similar between groups. A differential activation of MAPKs, as evaluated by MAPKs phosphorylation levels, was observed. Low levels of ERK1/2 activation and high levels of JNK and p38 activation were measured in fetal brain from the MZD group compared to the C group. Relative to controls, the AP‐1‐DNA binding activity in MZD fetal brain was significantly higher than in controls. These results show that marginal zinc nutrition imposed to rats during gestation affect MAPKs modulation and AP‐1 activation in E19 fetal brain. The pattern of MAPKs activation is similar to that previously observed in zinc deficient neuronal cells. Thus, alterations in MAPKs and AP‐1 activation could underlie the adverse effects of Zn deficiency on neurodevelopment. Supported by grants from the University of California, Davis, and NIH (HD 01743).
ZnT‐1 protein expression or localization does not explain effects of reduced availability of zinc on cellular zinc efflux
Authors: Dutta Amrita , Sankavaram Kavitha , Grattan Bruce , Freake Hedley C
Published: June 2021

Reducing zinc availability to H4IIE rat hepatoma cells with the extracellular chelator DTPA (diethylenetriaminepentaacetic acid) results in the rapid inhibition of cellular zinc efflux. In contrast, DTPA increases zinc efflux in primary hepatocytes. The SLC30 or ZnT group of membrane transporters is responsible for reducing cytoplasmic zinc, both via cellular efflux and organelle uptake. ZnT‐1 is believed to be key for zinc efflux, due to its reported plasma membrane localization. However, we found that DTPA does not change the concentration of ZnT‐1 mRNA or protein in H4IIE cells. Since cells could also control efflux by shifting the cellular location of ZnT‐1, we incubated H4IIE cells and primary hepatocytes with DTPA (50μM) or zinc sulfate (100 μM) for 2 hours and examined ZnT‐1 localization using immunocytochemistry. The distribution of ZnT‐1 immunofluorescence, which was observed throughout the cytoplasm, did not change with treatment in either cell type. We also treated H4IIE cells with DTPA or zinc and isolated plasma membrane proteins, following biotinylation and avidin purification. Neither DTPA nor zinc affected the amount of ZnT‐1 recovered in the biotinylated fraction as assessed by Western analysis. Thus we conclude that the rapid homeostatic response of cells to altered zinc availability must be attributed to a transporter other than ZnT‐1 or to changes in the activity of ZnT‐1 by a novel mechanism.
Zinc deficiency impairs neuronal STAT1 and STAT3 nuclear translocation through oxidant‐mediated mechanisms.
Authors: Aimo Lucila , Mackenzie Gerardo G , Oteiza Patricia I
Published: June 2021

Transcription factors STAT1 and 3 are involved in neuronal proliferation, survival and differentiation during development. Zinc (Zn) deficiency can lead to alterations in neonate and infant behavior, cognitive and motor performance that persist into adulthood. Therefore, we studied the effects Zn deficiency on STAT1 and 3, characterizing the role of oxidants and the cytoskeleton. The incubation of human neuroblastoma cells in Zn deficient media led to STAT1 and 3 activation that was inhibited by the antioxidant (±)‐α‐lipoic acid suggesting the involvement of oxidants in this process. However, a decrease in Zn levels led to an impaired transport of the active STAT1 and 3 from the cytosol into the nucleus. The relevance of the cytoskeleton for STAT nuclear transport was investigated. Vinblastine, colchicine or cytochalasin D impaired the nuclear transport of STAT1 and 3 indicating the need of a functional cytoskeleton. Similar data was obtained in E19 rat fetal brains, isolated from dams fed Zn deficient diets throughout gestation. Developmental Zn deficiency led to altered STAT1 and 3 nuclear translocations and a low in vitro fetal brain tubulin polymerization. Therefore, this study demonstrates the role of oxidants and the cytoskeleton in the modulation of STAT1 and 3, and the need of an adequate Zn status for their correct function in the nervous system. Supported by grants from UCDavis and NIH HD 01743.
A Randomized Double‐Blind Active‐Controlled Study of the Safety of UP165 and its Effects on Assessments of Depression, Anxiety and Well Being
Authors: Kalman Douglas S , Arencibia Karina , Feldman Samantha
Published: June 2021

This clinical trial compared the safety and effects of UP165, a dietary supplement that may be linked to mood function, with SAM‐e (s‐adenosylmethionine), a popular mood enhancing supplement. Assessments were made using the Beck Depression Inventory (BDI‐II), the Beck Anxiety Inventory (BAI), Schwartz Outcome Scale (SOS‐10) and Arizona Sexual Experiences Scale (ASEX). Forty‐two subjects (21–65 yo) were randomized to eight‐weeks of supplementation with UP165 or SAM‐e with questionnaires being administered at screening/randomization and weeks 4 and 8 of supplementation. Thirty‐four subjects were included in the efficacy analysis. There were no safety concerns raised by this study. UP165 and SAM‐e produced improvements in scores on the four questionnaires although no statistically significant differences were observed. UP165 was shown to be non‐inferior to SAM‐e with respect to depression (not within the ±8.35 equivalence tolerance interval) and equivalent to SAM‐e with respect to anxiety (fell within the ±6.4 equivalence tolerance interval). No superiority was noted between products. Future studies should examine increases in dose and or duration. A randomized double blind placebo‐controlled trial could strengthen the findings.

Funded by a grant from: Unigen Pharmaceuticals
A Modified Hop Extract (Meta060) Inhibits Hyperglycemia Mediated Monocyte‐Endothelial Interactions and LPS Mediated MMP‐9 Secretion in Human THP‐1 Monocytes
Authors: Desai Anuradha , Konda Veera Reddy , Bland Jeffrey , Tripp Matthew
Published: June 2021

It is now recognized that diabetes increases atherosclerosis complications by increasing the inflammation which activate matrix matalloproteinases (MMPs), causing instability in the plaque. Previously, we reported that various analogs of reduced iso‐alpha acid analogs have potent anti‐inflammatory properties in vitro. In this study, we evaluated the effect of Meta060, a modified hop extract on hyperglycemia mediated activation of monocyte, THP‐1 cells. Subjecting THP‐1 cells to hyperglycemic conditions activated the binding of THP‐1 to human aortic endothelial cells (HAEC). We found that Meta060 reduced the hyperglycemia mediated monocyte interactions to HAEC. We also evaluated the effects of Meta060 on LPS activated matrix metalloproteinase secretion in THP‐1 cells. Meta060 dose dependently reduced the expression and activity of MMP‐9 in THP‐1 cells. To understand the cell signaling pathways, we evaluated the Meta060 in cell free kinase assays. Meta060 dose dependently inhibited kinases involved in inflammatory signaling pathways, PKC, MAPK and NF‐κB. The data demonstrated that Meta060 inhibits inflammation in monocytes, monocyte‐endothelial interactions, and reduces monocyte MMP‐9 production, which could prevent the destabilization of plaque. These results suggest that Meta060 may be a useful treatment to reduce complications related to atherosclerosis (Supported by Metagenics Inc.)
Consumption of Green Tea Bioactive Compounds Alters Expression of Inflammatory Cytokine mRNA
Authors: Rowe Cheryl A. , Nantz Meri P. , Herrlinger‐Garcia Kelli A. , Knutson Mitch D. , Bukowski Jack F. , Percival Susan S.
Published: June 2021

In a human study, we previously showed that consumption of capsules containing L‐theanine and a standardized amount of catechins (Green Tea Formula, GTF) for 21d resulted in fewer cold symptoms, increased γδ T cell proliferation, increased interferon‐γ secretion and reduced blood levels of serum amyloid alpha, an inflammatory biomarker. A targeted microarray analysis of PBMC cultured 24h with ethylamine (EA) identified changes in mRNA expression in subjects who consumed the GTF capsules. Quantitative RT‐PCR analysis verified higher levels of interferon‐γ and CCL3L1 mRNA expression in EA‐stimulated cells after GTF intake compared to before consumption, consistent with the idea that the immune cells were primed by GTF. Levels of CCL5 did not change, nor did levels of CD4 or IL‐7 mRNA. Consumption of GTF reduced CSF‐receptor 1 expression in non‐stimulated cells. CSF‐R1 expression is associated with survival of mature monocytes; down regulation promotes apoptosis and perhaps reduces inflammation. We conclude that this formulation based on green tea bioactive components will prime immunity without promoting inflammation. Funded in part by UF/IFAS Agriculture Experiment Station, Nature Trade Center, Inc., and Taiyo International, Inc.
Variability in caffeic acid protection from dextran sulfate sodium‐induced colitis in mice
Authors: Ye Zhong , Hong Chung‐Oui , Lee Kwangwon , Hostetter Jesse , Wannemuehler Michael , Hendrich Suzanne
Published: June 2021

To examine interindividual variability in the efficacy of caffeic acid protection against colitis, 36 10‐wk‐old CD‐1/IGS female mice were fed 120 mg caffeic acid/kg diet for 7 d, with 12 controls fed AIN93G diet. Half of the mice in each treatment were then given 1.25% dextran sulfate sodium (DSS) in drinking water for 5 days. Caffeic acid prevented mouse body weight loss by DSS (p < 0.05). Colon lengths in mice fed caffeic acid/DSS were longer than in DSS‐treated control. Myeloperoxidase (MPO) was inhibited in mice given caffeic acid/DSS compared with DSS‐treated controls. Cecal score (necrosis, edema, erosion and neutrophil infiltration) of DSS‐fed mice was significantly more severe compared with mice fed caffeic acid before and during DSS treatment. Two subgroups were identified after cluster analysis of cecal score in mice fed caffeic acid/DSS. Mice with severe cecal damage showed mean cecal score of 9.1 (n=8), greater than did mice showing mild cecal damage (mean score=5.6, n=7, p <0.05). Caffeic acid‐fed mice with severe cecal damage had significantly greater colonic MPO activity than did mice with mild cecal damage (p <0.05). These effects in mice fed caffeic acid/DSS are hypothesized to be due to differences in caffeic acid bioavailability, which is under analysis.

Funded by Iowa State University Center for Designing Foods to Improve Nutrition.
Green tea formulation modulates catechin in vitro bioaccessibility and bioavailability in Sprague‐Dawley rats
Authors: Peters Catrina M. , Green Rodney J. , Janle Elsa , Ferruzzi Mario G.
Published: June 2021

To characterize the impact of green tea formulation on catechin bioavailability, 50 mg of green tea (GT) extract providing 3.8, 1.8, 1.5, and 2.5 micromoles of epicatechin (EC), epigallocatechin (EGC), epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) respectively was formulated plain (GT), with sucrose (GTS, 1.3g), and with sucrose plus ascorbic acid (GTS+AA, 10mg). Catechin digestive stability and intestinal uptake were assessed using a coupled in vitro digestion/Caco‐2 cell model. In vivo bioavailability was investigated in Sprague Dawley rats by 6h oral pharmacokinetic (PK) study. Catechin levels were measured by RPC18 HPLC. Addition of AA significantly (p<0.05) increased catechin in vitro digestive recovery (20 to >75%) with greatest impact on EGC (5 to >90%) and EGCG (6 to >61%). Caco‐2 intracellular accumulation of EGC was significantly increased to 70 pmol/mg protein by formulation with AA, compared to undetectable levels in GTS formulations. In vivo plasma PK data suggest that bioavailability of digestively labile EGCG and EGC may be enhanced by formulation with AA (AUC= 310 and 2671 nmol/mL respectively) relative to controls (AUC = 195 and 2346 nmol/L respectively). These data provide evidence that formulation factors impact both digestive recovery and may influence intestinal absorption of catechins from tea beverages in vivo. (Supported by NIH NCCAM grant P50‐AT00477)
High Fruit and Vegetable Intakes are Associated with Lower Homocysteine Levels in Cuban‐Americans
Authors: Zarini Gustavo , Gomez Gianna Perez , Nath Subrata , Huffman Fatma G
Published: June 2021

We examined the relationship between fruit and vegetable intake with homocysteine (HCY) levels in Cuban‐Americans with (n=182) and without (n=166) type 2 diabetes mellitus (T2DM). Subjects were randomly recruited from Miami‐Dade and Broward Counties, Florida. HCY levels were analyzed from fasting blood. Dietary intakes were determined using FFQ. Reported fruit and vegetable intakes were summed to obtain a single variable. Subjects were divided into quartiles for total fruit and vegetable intake. Statistical analyses used SPSS and included descriptive statistics, multinomial logistic regression and ANCOVA, controlling for age, gender, T2DM status, hypertension status, BMI, smoking, alcohol, total energy, folate and vitamin B12 intakes, vitamin supplement use (multivitamins, folate and vitamin B12). Mean fruit and vegetable intake differed significantly (all p‐values<.001) across quartiles, with values of 7.0, 10.5, 13.2, and 15.4, respectively. T2DM subjects were more likely than non‐diabetics to be in the lower and median quartiles of fruit and vegetable intake, p<.05. After adjustment for potential confounders, subjects in the 2nd quartile had significantly higher HCY levels than subjects in the 4th quartile, p=.034. However, post hoc analyses revealed that this was true only for non‐diabetics. Higher intakes of fruits and vegetables in Cuban‐Americans are associated with lower HCY levels.
Effect of CLA isomers on renal injury in the obese fa/fa Zucker rat
Authors: Zhan Yang , Aukema Harold M. , Taylor Carla G. , Zahradka Peter C. , Ogborn Malcolm R.
Published: June 2021

Obesity is associated with greater risk and incidence of nephropathy. Mixed conjugated linoleic acid (CLA) isomers have beneficial effects on renal disease, but the effect of individual CLA isomers is not known. Our objective was to test whether dietary CLA isomers would alter renal injury progression in the obese fa/fa Zucker rat. Male obese and lean 17 wk old fa/fa Zucker rats were given diets with either 0.4% c9, t11 CLA, 0.4% t10, c12 CLA or control diet for 8 wk, after which renal function and histology were assessed. The dietary t10, c12 CLA decreased the glomerular volume, worsened the glomerulosclerosis and increased macrophage infiltration compared with control. In the t10, c12 CLA group, there was a trend for increased kidney weight, proteinuria, kidney fibrosis and tubular injury (tubular atrophy, calcification and casts) and reduced creatinine clearance, but these were not statistically different from control. The dietary c9, t11 CLA group had smaller glomeruli than control, and less glomerulosclerosis, fibrosis and macrophage infiltration compared with the t10, c12 CLA group. Hence, t10, c12 CLA exacerbates renal injury associated with obesity, while c9, t11 CLA does not, and may be protective. (Supported by Manitoba Agriculture Food and Rural Development Initiative, Dairy Farmers of Canada and NSERC)
Comparative impact of tart cherry‐enriched diets on metabolic syndrome and inflammation in rats fed high versus low carbohydrate diets
Authors: Seymour E Mitchell , Urcuyo‐Llanes Daniel , Kirakosyan Ara , Kaufman Peter B , Bolling Steven F , Bennink Maurice R
Published: June 2021

Previous studies show that diet provision of anthocyanin‐rich extracts reduces phenotypes of metabolic syndrome. Our group tested the dietary relevance of these findings using a whole‐foods approach with anthocyanin‐rich tart cherries. We compared the effects of tart cherry‐enriched diets in lean Zucker rats, isocalorically pair‐fed a low‐fat/high carbohydrate diet (LFHC, 10% kcal from fat, 75% from carbohydrate) versus a high‐fat/moderate carbohydrate diet (HFLC, 45% kcal from fat, 40% from carbohydrate). Diets were supplemented with either 1% freeze‐dried tart cherry powder or 0.85% extra carbohydrate (1:1 glucose:fructose). Measures include fasting glucose, total triglycerides, total cholesterol, insulin, plasma IL‐6 and TNF‐alpha, organ weights, and fat pad mass. Results showed that the cherry provision reduced cholesterol in both diets. The LFHC diet significantly increased plasma triglycerides, an effect that was significantly attenuated in cherry‐fed rats. While cherry provision did not affect body weight, cherry was associated with reduced the visceral fat in LFHC‐fed rats. Cherry‐fed rats also displayed reduced IL‐6 and TNF‐alpha in the HFLC‐fed rats. The findings suggest that tart cherry‐enriched diets reduce plasma triglycerides, central adiposity, and systemic inflammation, known risk factors for Type II diabetes and cardiovascular disease.
Blood pressure lowering effect of Monascus starter fermented soy product in Spontaneously Hypertensive Rats
Authors: Chang Moon‐Jeong , Choi Pok‐Su , Kwon Ji‐Youn , Kim Sun‐Hee
Published: June 2021

The present study was carried out to evaluate the effect of dietary soy product(SP) and Monascus starter fermented soy product(MS) on blood pressure(BP), angiotensin converting enzyme(ACE) activity and sodium(Na) balance in spontaneously hypertensive rat(SHR). Twenty‐week‐old SHRs(n=18) were randomly blocked into three groups according to the blood pressure(BP) and fed for 4 weeks either a diet containing casein(CO), SP or MS, respectively. The changes of systolic blood pressure were measured by tail‐cuff method and ACE activities of serum, lung and kidney were analyzed. The subsequent fecal and urinary excretions of Na were measured by ICP‐atomic emission spectrometry. The systolic BP of MS was lower than that of the control group(p<0.05). ACE activity of lung was lower in SP group than that of CO group(p<0.05), although those of serum and kidney were not affected by experimental diets. After feeding MS, significant increase in fecal Na excretion and decrease in Na retention were observed(p<0.05). Urinary Na excretion was not affected by SP or MS in SHRs. These results suggest that Monascus starter fermented soy product produce an antihypertensive effect that may be mediated by inhibiting Na absorption in gastrointestinal tract and decreasing Na retention.

This study was supported by 2006 Seoul B&RD program.
The prevalence of favorable PTEN and MGMT biomarker status in 66 glioblastomas
Authors: de Jesus Jason A , Lam Diana N , Tinajero Yolanda L , Kavafyan Lorie , Zhang Haijing , Taieb Philippe , Deguzman Victoria C , Mischel Paul S , Cloughesy Timothy F , Yong William H
Published: June 2021

Glioblastomas are genetically heterogeneous neoplasms with variable responses to therapy. Biomarkers that predict response to therapy include O6‐methylguanine‐DNA methyl transferase (MGMT) and phosphatase and tensin homolog (PTEN). MGMT is a DNA repair enzyme and low levels of MGMT expression in tumors have been associated with response to Temazolamide, an alkylating agent. PTEN is a phosphatase that modulates signaling pathways downstream from EGFR and loss of PTEN predicts a poor response to small molecule EGFR kinase inhibitors. In this study, we attempt to assess the prevalence of a favorable biomarker status in 66 glioblastomas. The glioblastomas are sampled in triplicate on a tissue microarray. Sections are then assayed for MGMT and PTEN by immunohistochemistry. The extent of tumor cell staining is semi‐quantitatively scored as percentages. PTEN loss greater than 25% is considered deficient as previously reported. By published criteria, MGMT immunostaining in less than 20% of tumor cells is considered favorable. 72.7% (48/66) of the tumors have a favorable PTEN status. 37.8% (25/66) have a favorable MGMT status. 27.3% (18/66) of the glioblastomas have both a favorable PTEN and MGMT status. Therefore, only a minority of patients are predicted to have available two lines of therapy. To avoid use of possibly ineffective therapies, more work is needed to identify other predictive biomarkers.
Metastasizing breast carcinoma to the brain: a clinicopathologic and immunohistochemical study of 14 matched pairs.
Authors: Hattab Eyas M. , Cheng Liang , Al‐Khatib Sohaib M , Steeg Patricia S
Published: June 2021

Brain metastasizing breast cancer is the second most common cause of brain metastases. The frequency of brain metastasis ranges between 10‐40% of breast cancers. Hormonal status of the primary malignancy is thought to play a role in determining which tumors eventually will show brain metastasis. In this study, we examined 14 pairs of matched primary breast carcinomas and their respective brain metastases for various clinicopathologic parameters and performed immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), Her‐2/neu, and epidermal growth factor receptor (EGFR). The mean age at diagnosis of breast primary and the subsequent brain metastases was 54.8years (36–74) and 57.7years (39–75), respectively. The mean interval between the diagnosis of breast carcinoma and the brain metastasis was 32 months (4 months–8 years). All 14 breast primary cancers were of the invasive ductal type and over half (8/14) were high grade (SBR III/III). Nine (64%) of the matched pairs were ER negative and 10 (71%) were PR negative but only 7 (50%) were both ER/PR negative. Three (21%) pairs were found to be Her2/neu positive by immunohistochemistry. Overall, 5 (36%) matched pairs were “triple negative”. Diffuse and strong EGFR immunoreactivity was observed in 4 primary breast cancers and only 2 brain metastases. Both EGFR positive brain metastases had EGFR positive primaries. EGFR‐ positive pairs were more frequently “triple negative” or in one case, ER/PR negative and Her2/neu positive. Her2/neu analysis by FISH is underway.
Metastatic Papillary Thyroid Carcinoma in Brain: Report of Three Cases
Authors: Li Jianyi , Aldape Kenneth D , Fuller Gregory N , Powell Suzanne Z
Published: June 2021

Background:

Papillary thyroid carcinoma (PTC) is the most common thyroid neoplasm. PTC generally carries a good prognosis since it is usually confined to the thyroid and tends to metastasize to regional lymph nodes (ex. cervical and upper mediastinal nodes). Distant metastases occur in only 5 to 14% cases. Brain metastases are extremely rare, occuring in 0.1 to 5% of reported cases. We report 3 cases of total thryoidectomy (TT) for PTC followed by subsequent brain metastases.

Case reports:

69‐year‐old man treated with TT, radiation therapy and radioactive iodine six and half years ago who presented with acute onset of headache. MRI showed lesions in right temporal and occipital lobes.

64‐year‐old woman underwent TT more than 15 years ago and presented with a mass in the left temporal lobe involving the lateral ventricle.

50 year‐old man underwent TT 2 years ago and presented with a mass in right frontotemporal lobe.

Tissue sections in all cases showed metastatic papillary carcinoma immunoreactive for thyroglobulin and TTF‐1.

Conclusion:

In general, central nervous system metastases from PTC are associated with high mortality rates. Resection of single metastasis to brain or irradiation of multiple lesions improves long‐term outcome. In patients with brain metastases with unknown primary which exhibit papillary architecture, thyroid origin should be considered in the differential diagnosis.
Evaluation of hormone receptor status and proliferation with a novel isoform of proliferating cell nuclear antigen (ca‐PCNA) in predicting recurrence of pediatric meningioma
Authors: Rushing Elisabeth J. , Agarwal Beamon , Man Yao‐Go , Santi Mariarita , Comeaux Jarmon C. , Hickey Robert J. , Malkas Linda H.
Published: June 2021

BACKGROUND

Meningiomas are uncommon in children and experience is limited compared to their adult counterparts. Predicting recurrence does not reliably correlate with tumor grade.

PURPOSE: To review hormone receptor status and proliferation in 13 cases of intracranial meningioma in children.

METHODS AND MATERIALS: Clinicopathologic data were reviewed on thirteen patients (6 females, 7 males) treated for meningioma during a 19‐year period. The patients ranged in age from 8–20 (mean, 15.2 years; SD, 4) years at the time of diagnosis. In all cases, estrogen and progesterone receptor, proliferating cell nuclear antigen (PCNA), ca‐PCNA and Ki‐67 status were analyzed using immunohistochemistry on formalin fixed paraffin sections. On initial biopsy, all meningiomas were grade I, WHO 2007.

RESULTS: Four patients developed recurrent disease after a latency period of 1–3 years (mean, 1.6 years, SD, 0.9). The mean Ki‐67 proliferative index was 1; overall, PCNA ranged 10–90% (mean, 66.7) and ca‐PCNA ranged from 10–90 (mean, 32.5). Mean ca‐PCNA value in recurrent meningiomas was 47.2% while in non recurrent it was 17.8%. Staining for hormone receptors revealed that 1–90% of cells expressed progesterone (mean, 34.6%) and none labeled with estrogen.

CONCLUSION: There is a positive correlation between ca‐PCNA expression with meningioma recurrence in children.