bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards the Nitric Oxide Reductase Mechanism of Flavodiiron Proteins
Authors: Frederick Rosanne , Kurtz Donald M.
Published: June 2021

Flavo‐diiron proteins (FDPs) catalyze reductive scavenging of molecular oxygen and nitric oxide in air‐sensitive microorganisms. The flavin cofactor in close proximity to the diiron site distinguishes FDPs from other non‐heme diiron proteins. FDPs from various sources catalyze dioxygen reduction or nitric oxide reduction (NOR) to varying degrees, and questions arise as to how the active site optimizes levels of the two activities and about what structural features affect the catalytic mechanism of FDPs. Published studies have identified diferrous mononitrosyl and diferrous dinitrosyl complexes for the FDP from Thermotoga maritima (TmFDP). An NOR mechanism consistent with these results consists of reduction of a diferrous‐dintrosyl adduct by the proximal reduced flavin prior to N‐N bond formation and release of N2O. In attempts to determine the reasons for the varying NOR activities in FDPs, we are conducting analogous studies on the FDP from Moorella thermoacetica (MtFDP). The reported turnover number for NOR activity in MtFDP is ~1000‐fold greater than that of TmFDP. Rapid kinetics studies are in progress to identify NO complexes in the higher‐activity MtFDP.
Orfila museum in Paris “Booklet of the Museum of Normal Anatomy”, Masson, 1865
Authors: LE FLOCH‐PRIGENT Patrice Pierre
Published: June 2021

A “Booklet of the Museum of Normal Anatomy”, was published by Victor Masson and son(s) in 1865 in Paris. It was a repertoir of the samples of the Orfila's museum in Paris, very probably finished in the beginning of 1863 (as authentified by the preface by J. MMaissiat, the curator and certainly the main author). It was reduced in size (12,3 × 18,7 cm) and short (123 pages). It was divided in four parts : organs of the external life (relation), of the internal life (organical), of the generation, development of the organs. It will be followed by the catalogue of Charles Houel in 1880, Paris, Masson; and the catalogue of “Surgical and Radiological Anatomy” in 1995, Springer Verlag. The Orfila's museum vanished from Paris in 2009. This booklet is very interesting as the authors of the models were noticed when they were known.
AGGREGATED PROTEINS? LET's PUT A CAP ON THAT! Exploration of the GroEL‐GroES‐(ADP)7 Chaperonin Complex
Authors: Baker Jessica , Bold Kylie , Briley Andrew , Eaton Muriel , Geick Dylan , Richards Megan , Rowland Daryle , Scheafer Tim , Kessler Eric , Tuel Kelly , Whalen Joseph
Published: June 2021

Sickle cell anemia, cystic fibrosis, and Alzheimer's disease are each associated with misfolded proteins. Most proteins fold into their functional state spontaneously and unaided, but they can become trapped in misfolded states harmful to human health. Chaperones are proteins that assist such proteins in folding or refolding successfully. The Blue Valley CAPS 2012–13 SMART Team (Students Modeling A Research Topic) modeled the asymmetric GroEL‐GroES‐(ADP)7 chaperonin complex, (1AON.pdb), using JMol and their 3D printer. The chaperonin complex is shaped like a hollow bullet with identical heptameric GroEL trans and cis subunits positioned back‐to‐back, with a heptameric GroES subunit capping the later. When functioning, a misfolded protein bonds to hydrophobic residues lining the rim of the uncapped GroEL cis subunit. ATP binding to this subunit results in conformational changes that release the protein into a now expanded space as it becomes capped with GroES. Then, newly exposed hydrophilic residues encourage the proper folding of the confined protein. ATP hydrolysis in GroEL cis, and subsequent ATP binding in the GroEL trans, promote the disassociation of the GroES cap and the release of the properly folded protein. An understanding of mechanisms supporting protein folding will help in the development of treatments for diseases associated with misfolded proteins. Supported by a grant from NIH‐SEPA.
Heterogeneity Studies of Cyrtophora citricola in Puerto Rico
Authors: Cardona Jaime , Arroyo Nancy , Asencio Carmen
Published: June 2021

Cyrtophora citricola is a spider originally from Africa. It has been found in Colombia (1996), Haiti (1998), Florida, U.S. (2000), Cuba (2003), and more recently in Puerto Rico (2008). It has become an important organism for research due to its impact in agriculture. Recent studies have questioned whether this organism can be classified as only deleterious or whether it presents beneficial aspects for agricultural use. It is not known whether plants that serve as host are damaged by the spider or by the presence of the dense web. More than one spider can be found in a single spider web, a condition that is rare for spiders who exhibit a natural low tolerance level for other organisms, including those of their own species. In order to better understand this organism and its behavior, we decided to verify parental relationship between all the specimens of the same gender of C. citricola found in a single web. Female spiders genomic DNA was successfully extracted. A 710 bp fragment from the cytochrome c oxidase subunit 1 gene (CO1) was amplified by PCR. This gene is highly conserved making it suitable for heterogeneity studies among the different gender spiders collected from the same web and from different regions in Puerto Rico.
Yoga as an experiential learning tool to effectively teach musculoskeletal anatomy of the back and lower extremities
Authors: Tomson Allison , Zumwalt Ann
Published: June 2021

The concept of learning human anatomy through activity, specifically yoga and Pilates, can increase comprehension and understanding of the material being taught. This concept was pioneered in medical education in 2004 by two medical students with their director of Anatomy at the Mt. Sinai School of Medicine. Following their model, students at Boston University School of Medicine were offered a 1.5‐hour review of the musculature of the back and lower extremity, using yoga as an experiential learning tool. The workshop utilized active yoga poses to emphasize muscle action and stretching poses to highlight the origins and insertions of muscles and muscle groups of interest. Improvement in student's comprehension was measured using an online survey offered before and after the workshop including 10 questions directly addressed in the yoga anatomy module, and 5 related questions that were not specifically discussed in the yoga module, but were directly addressed in Anatomy lecture and/or lab. Post‐ survey analysis showed significant improvement in comprehension of the topics covered after the yoga anatomy review. There was also minimal improvement in the topics not addressed in the review. Additionally, students reported feeling more relaxed afterward and appreciated the opportunity to be active while studying, allowing them to effectively maximize their time.
Serum thioredoxin 1 levels in female patients with community‐acquired pneumonia
Authors: Kim Il‐Han , Cha Mee‐Kyung
Published: June 2021

Community‐acquired pneumonia (CAP) commonly causes acute respiratory failure with high mortality. Here, we report that in contrast to the serum HP, levels of Trx1 is significantly decreased in serum from patients with CAP, especially in serum from female CAP patients. The levels for Trx1 in serum samples from patients with CAP compared to healthy controls using an indirect ELISA assay method. We assess the correlations of Trx1 with haptoglobin (HP), a well‐known biomarker for CAP. The CAP detection ability of Trx1 and HP were evaluated using receiver‐operating characteristic (ROC) curve. Analysis of the ROC curves indicates that CAP detection ability of Trx1is comparable to that of HP. At the cut‐off point 0.3964 at A540nm on the receiver operating characteristic curve, Trx1 could well discriminate CAP from normal female controls with a sensitivity of 72.5%, specificity 89.8%, and area under the curve (AUC) 0.877+/−0.0395. Decreased serum levels of the Trx1 in female CAP patients were reversely correlated with the elevated serum levels of HP (P<0.05). Considering that elevated serum levels of Trx1 and HP in various diseases including carcinomas, the decreased serum Trx1 in case of female CAP patients may be helpful for the CAP‐specific diagnosis for female subjects. *This work was financially supported by project B0009735) funded by the Ministry of Knowledge Economy of Korea.
Effects of a high fat diet and Metformin on skeletal muscle membrane proteins and fiber size in young mice
Authors: Botchlett Rachel E , Woo Shih‐Lung , Xu Hang , Li Honggui , Wu Choadong , Lawler John
Published: June 2021

A prolonged high fat diet (HFD) is known to impair insulin signaling in skeletal muscle. Specifically, HFD reduces caveolin‐3, Akt activation, and GLUT‐4 translocation to the membrane. Type II diabetes results in the loss of sarcolemmal proteins of the dystrophin‐glycoprotein complex (DGC), particularly dystrophin and nNOS. However, the effect of HFD on DGC proteins is unknown. We hypothesized that HFD would cause translocation of DGC proteins away from the membrane. We further postulated that Metformin, an oral anti‐diabetic drug, would alleviate translocation of DGC proteins. To test our hypotheses, 8 week old C57Bl‐6 mice were fed a high fat diet for 14 weeks (n=8). After 9 weeks, mice were also given either PBS (n=4) or Metformin (n=4) for the remaining 5 weeks. Soleus muscle fiber cross sectional area (CSA) and DGC protein expression were quantified using immunohistochemistry assays. Surprisingly, we found a marked increase in fiber CSA that was normalized by Metformin. HFD resulted in a small decrease of dystrophin membrane expression with no change in nNOS, while the Metformin group expressed normal levels. These findings indicate that the DGC may undergo only minor functional changes in young mice fed a short term HFD, which are similar findings seen with muscle fiber hypertrophy. We postulate that intact DGC proteins may help preserve insulin signaling during short term HFD. Our future research will therefore focus on understanding how insulin signaling (e.g., IRS‐1, mTOR) might be preserved, and the point at which intact muscle insulin pathways in young mice become perturbed with prolonged HFD. This work was supported in part by ADA grant 1–10‐JF‐54 and AHA 12BGIA9050003 (to C.W).
The utilization of sulfur amino acid in the mercapturate pathway to detoxify maximal therapeutic dose of acetaminophen is associated with glutathione and protein homeosteny in adult rats
Authors: Mast Carole , Joly Charlotte , Martin Jean‐François , Dardevet Dominique , Pujos‐Guillot Estelle , Papet Isabelle
Published: June 2021

It has been shown that sulfur amino acids (SAA) used for acetaminophen (APAP) detoxification, as sulfate conjugate and mercapturate (glutathione (GSH) conjugation), can represent a significant part of dietary SAA and lead to GSH and protein homeosteny. We determined the metabolic alterations induced by APAP detoxification in adult rats receiving daily the half or maximal therapeutic French dose for human. APAP was provided in a 16% protein diet at the dose of 0 (control, n=6), 0.5 (n=7) or 1% (n=7) for 17 days. 1% APAP reduced nitrogen balance (36%), weights of small intestine (13%) and gastrocnemius (7%), hepatic, muscular and intestinal GSH levels by 56%, 20% and 8%, respectively. These parameters were unchanged by 0.5% APAP. Urinary sulfate conjugate was independent of APAP dose, whereas mercapturate of APAP increased from 3% to 14% of ingested SAA in 0.5 and 1% APAP, respectively. Posttranslational alterations of hepatic proteins (APAP protein adducts and modified residues, assessed by target and global metabolomics) occurred with 0.5% APAP and to a larger extent with 1% APAP. Variations of all studied parameters occurred with the APAP dose that is accompanied by upper use of SAA. Further experiments are required to determine if cysteine supplementation could preserve the structure of hepatic proteins at moderate APAP dose, and limit all metabolic alterations occurring with the APAP dose at 1% of the diet.
Body composition, energy metabolism and endocrine variables in weight stable gastric‐bypass patients
Authors: Holmback Ulf , Berglund Marie , Cederholm Tommy , Sundbom Magnus
Published: June 2021

Background

Despite the vast number of weight reducing operations performed, knowledge is still scarce regarding more long term metabolic alterations caused by the operations.

Aim of the study

To investigate the relationships between various body composition as well as endocrine variables in weight stable GBP operated patients.

>;Subjects and methods

Formerly GBP‐operated but weight stable women (16) and men (4)(Age 48.9 ± 8.1 y; BMI 33.1 ± 1.9 kg/m2) were admitted to the laboratory after an overnight fast. Respiratory exchange ratio (RER), body composition and several endocrine variables were analyzed. RER, waist circumference, DXA % fat, and insulin were used as main variables, and correlations were calculated with all other variables.

Results

Mean fasting RER was high (0.88±0.07) and did not correlate with any other measured variable. Waist circumference was large (109±9 cm) and correlated only with BMI, RMR and fat mass. DXA % fat was high (43.8±5.6%) and correlated only with body composition values from BodPod, as well as RMR. Insulin was in the normal range (9.4±3.0 pU/L) and correlated with age, height/waist ratio, BMC, glucose and ApoB/ApoA1‐ratio.

Conclusion

The correlations observed, or sometimes lack of correlation, also shows that despite being weight stable for at least three years, the GBP‐subjects still show some metabolic irregularities.
Association of inflammatory markers with cognitive, pain and functionality assessment measures in long term care older adults
Authors: Viveky Navita , Billinsky Jennifer , Thorpe Lilian , Alcorn Jane , Hadjistavropoulos Thomas , Whiting Susan
Published: June 2021

Chronic inflammation may promote the development of age related conditions such as dementia, osteoporosis, pain and frailty especially in long term care (LTC) residing older adults. Aim of the study was to determine associations between inflammation and measures of functionality, cognition and pain in LTC residing older adults in Saskatoon, SK Canada. Those 60–80 y residents in LTCs, able to satisfactorily comply with protocol requirements were enrolled. Blood draws (inflammatory cytokines, hs‐CRP, 25(OH)‐vitamin D, cholesterol and prealbumin), vital signs, chart review and functional assessments (cognition, physical functioning, and pain) were done at baseline. Correlational analysis was used to study the relationship of inflammatory markers with the cognitive, functional and pain indices. Adults (n=26; 8 F, 18 M) (mean age 70.7 y) were enrolled. IL‐6 was significantly inversely correlated to all physical functioning measures. hs‐CRP was inversely correlated to cognitive tests (r = −0.54, p < 0.05) and activities of daily living (r = −41, p < 0.05). 25(OH)D was positively correlated to grip strength (r = 0.43, p < 0.05). Pain measures showed no significant correlations. Our results indicate an association of inflammatory markers with functionality tests, particularly grip strength, cognition, and activities of daily living in the LTC residing older adults. SHRF grant to Dr.T. Hadjistavropoulos QOL Team.
Systematic Review and Meta‐Analysis of Food‐Based Interventions on Recovery from Moderate Acute Malnutrition in Young Children
Authors: Suri Devika , Moorthy Denish , Rosenberg Irwin
Published: June 2021

Background and Objective

The rationale of this systematic review was to examine the comparative effectiveness of lipid‐based nutrient supplements (LNS) versus fortified blended foods (FBF) in treatment of moderate acute malnutrition (MAM).

Data sources

All published articles identified though MEDLINE® and Cochrane Central Register of Controlled Trials, from inception to July 2012.

Study selection

Reviewers independently selected eligible comparative studies of children under 5 with MAM. Interventions were broadly categorized as FBF or LNS.

Data extraction

Article information was extracted using a standardized protocol into predesigned forms and reviewed for accuracy.

Results

34 out of 12,453 screened articles were accepted. Interventions ranged 8 to 16 wks. Meta‐analysis of 5 studies showed a 10% lesser recovery rate from MAM in children treated with FBF as compared with LNS (RR=0.9, 95% CI 0.8,1.01; 79.6% LNS vs 77.5% FBF). This indicates that for every 48 children that are treated with FBF rather than LNS, one child will not recover from moderate malnutrition.

Conclusions

LNS is associated with a higher rate of recovery from MAM when compared with FBF. The studies on children with MAM are heterogeneous leading to dilution of comparative effect. The clinical relevance of outcomes as well as cost‐effectiveness need to be taken into consideration when interpreting the results.
Women who participate in a structured weight loss program with resistance‐exercise experience more favorable changes in blood lipids when compared to other popular weight loss programs
Authors: Galvan E , Lockard B , Baetge C , Levers K , Jagim A , Simbo S , Byrd M , Jung YP , Oliver JM , Koozehchian M , Dalton R , Khanna D , Sanchez B , Kresta JY , Horrell K , Leopold T , Cho M , Springer S , Rivera A , Cerda C , Rasmussen C , Kreider R
Published: June 2021

123 sedentary women were randomized into a control group (C), Curves Complete® (CC), Weight Watchers® (WW), Jenny Craig® (JC), or Nutrisystem® (NS) weight loss program for 12‐wks. Fasting blood samples were obtained at 0, 4, 8, & 12 wks. Data are percent changes from baseline. Significant group × time interactions were observed in TG (C −2.2±29, −7.7±26, 0.1±24; CC −27.1±21, −24.2±24, −23.2±20; WW −8.5±32, 1.6±36, −2.7±31; JC 3.3±40, 8.0±34, 15.1±43; NS 6.9±39, 11.2±33, 11.1±29 %, p=0.002) and HDL‐c (C 0.6±11, −3.5±10; −5.0±10; CC −0.8±11, 0.3±11, 5.0±15; WW −5.1±12, −4.0±13, 0.2±14; JC −10.9±12, − 6.4±14, −5.0±16; NS −6.2±14, −6.5±12, −4.0±13 %, p=0.01). Total CHL tended to differ among groups (C 0.6±12, −0.3±12; −2.2±11; CC −11.8±11, −9.1±9, −7.5±11; WW −5.8±12, −2.8±12, 0.6±12; JC − 7.2±13, −3.3±13, −2.3±11; NS −4.9±13, −4.5±12, −3.8±16 %, p=0.07). No differences were observed among groups in LDL‐c (C −1.9±18, 1.7±23; −4.0±17; CC −11.1±15, −9.2±13, −7.8±19; WW − 1.4±20, 1.6±23, 10.4±51; JC −6.5±17, −1.7±17, −2.7±12; NS − 4.6±18, −5.5±14, −6.1±21 %, p=0.21) or blood glucose (C 1.7±8, 2.6±6; −1.3±8; CC −2.2±10, −1.9±8, −2.4±12; WW −1.5±12, −1.1±9, −1.7±8; JC −3.3±9, −2.4±11, −1.6±10; NS −0.8±16, −3.2±14, −2.9±16 %, p=0.91). Results reveal a high protein/low fat weight loss program with resistance‐training promotes more favorable changes in blood lipids compared to some other popular weight loss programs.
Resource management behaviors and strategies among low‐income individuals
Authors: Wasson Amy , Anliker Jean , Peterman Jerusha Nelson
Published: June 2021

Food insecurity may lead to micronutrient inadequacies with constrained resources and increased caloric intake with available resources. Resource management skills can mitigate the effects of concurrently limited and inconsistent resources. Data on actual dietary behaviors and coping strategies are limited. We analyzed 6 focus group transcripts (21 participants) with low‐income, largely food insecure individuals in Massachusetts to describe dietary practices and assess related resource management strategies. We used directed content analysis to examine pre‐identified themes and identify new themes within cyclic resources affecting food choices. Some participants reported purchasing high‐calorie foods when resources were plentiful and when resources were constrained. Some purchased vegetables and fruits in times of higher resources. Others did not change purchases with cyclic resources, but reported strategies like using a budget and buying in bulk. Our work provides qualitative evidence that cyclic resources affect dietary practices. Additional resources could help individual's purchase the healthy foods that they want but cannot consistently afford. Nutrition education may mitigate disparities by providing tools to have consistent caloric and nutrient intake. Social safety net programs could target benefits to increase consistent consumption of healthy foods. USDA‐CSREES #H994.
Urban agglomeration and overweight prevalence in Indian urban population: Is there a link?
Authors: Chakraborty Priyanka , Mitra Chandana
Published: June 2021

Urbanization in developing countries has become a burning issue due to its impact on health, environment and lifestyle. It has been identified as a causal indicator of easy access to fast food and physical inactivity. In India the number of Urban Agglomerations (UA) have increased from 384 to 475 (2011 Census) indicating the staggering expansion of urban areas.

With this in view, the overarching goal of this study will be to determine the association between urban growth patterns in five UAs of India (Mumbai, Delhi, Kolkata, Chennai and Bangalore) with the extent of overweight prevalence among adults residing in these mega‐cities (women: n = 26318; age: 30.85 ± 8.75 years; men: n = 9965; age: 32.3 ± 10.05 years). We will use data from the three waves of the National Health and Family Survey (NFHS) of India ranging from 1992–2006. The three objectives will be i) to estimate the prevalence of overweight amongst adults in the five UAs; ii) to examine the correlation between population growth rate patterns within the UAs (using decadal census data), rural‐urban migration and changing socio‐economic patterns; iii) to examine the independent association between population growth rate and overweight prevalence using hierarchical regression models. The outcome of this study will emphasize the urgency to educate the urban communities about obesity/overweight issues through tailored nutrition programs.

Funding: Dept of Nursing and Nutrition, State University of New York College, Plattsburgh
Stevia –a natural sugar substitute‐ attenuates endothelial dysfunction induced by hypercholesterolemia
Authors: Yilmaz Cigdem Erkuran , Latorre Johan , Yilmaz Gokhan
Published: June 2021

Stevia (Stevia rebaudiana) is a widely used plant‐based natural sweetener with no caloric value. Although there are reports suggesting that Stevia might cause vascular relaxation, the effects of dietary Stevia intake on vascular responses in hypercholesterolemia have not been addressed in the current literature. Our objective was to test whether Stevia leaf extract would attenuate endothelium damage associated with hypercholesterolemic diet.. C57BL/6 male mice were fed with high cholesterol diet either with or without dietary Stevia for 2 weeks. Stevia leaf extract was dissolved in drinking water (1.675g per L) and administered with drinking water ad libitum. The endothelium‐dependent vasodilation was tested using ex vivo wire myography. Endothelium‐dependent vasodilation was assessed as % relaxation to 10–6 acetylcholine at aortas precontracted with 10–6 phenylephrine. Dietary Stevia intake improved the impaired endothelial vasodilation induced by high cholesterol diet (high cholesterol diet % 38±9vasodilation vs high cholesterol + Stevia %59±7 vasodilatation: P< 0.05, t‐test with Welch's correction). Since Stevia is widely used as a food additive and dietary supplement our findings indicate an alternative vascular benefit of Stevia other than reducing the caloric intake as a substitute for table sugar.
Healthy Eating Index‐2005 Scores and Pulmonary Function
Authors: Root Martin , Houser Shannon , Gutschall Melissa , McAnulty Lisa
Published: June 2021

Introduction

A decline in pulmonary function is represented by decreasing FEV1/FVC (forced expiratory volume in one second/forced vital capacity). Diet is thought to impact pulmonary function.

Hypothesis

Higher Healthy Eating Index‐2005 (HEI‐2005) scores will correlate with elevated FEV1/FVC measurements.

Methods

The analysis was conducted using the Atherosclerosis Risk in Communities (ARIC) study. HEI‐2005 scores were based on food frequency questionnaire and nutrient value datasets. Multivariate linear regression was used to analyze the effect of HEI‐2005 scores on FEV1/FVC measurements while controlling for covariates.

Results

HEI‐2005 scores were not significantly correlated with FEV1/FVC. However, significant associations were observed for HEI component scores (p<0.001). FEV1/FVC was positively associated with total fruit, whole grains, milk, oils, sodium, and calories from solid fats, alcoholic beverages, and added sugars (SoFAAS) and negatively with vegetables and legumes, and meat and beans.

Conclusion

A correlation between HEI‐2005 scores and pulmonary function was not observed. However, FEV1/FVC was correlated with HEI‐2005 component scores, not always as expected.
Development and production of a nutritious biscuit from blends of food grains for prevention of protein ‐ energy malnutrition among school age children in low income countries.
Authors: Oluwole Oluwatoyin Bolanle , Oluwole Oluwatoyin Bolanle , Kosoko Babatunde Sulaimon
Published: June 2021

A simple process technology was developed for producing a high nutrient density biscuit using locally grown food crops such as yellow maize, white sorghum(cereal) and soybeans(legume) targeted for school aged children(6–13years). The flours from these crops were blended at the ratio of 35:35:25 cereal flours and full fat soyflour/low fat soyflour respectively. The flour blends were kneaded with other baking ingredients, with added mineral and vitamin premixes. The results of nutritional evaluation of the biscuit through animal feeding experiment studies revealed that the biological value of the developed biscuit was 99.8%, protein efficiency ratio was 3.10, net protein utilization was 99.5%. The product also supported weight gain in the experimental rats used. Heamatological results, liver function and kidney function tests showed that developed products were safe for human consumption and were not toxic.
Kimchi attenuates cellular oxidative stress induced by peroxynitrite
Authors: Cho Eun Ju , Kim Boh Kyung , Choi Ji Myung , Ahn Soon Cheol , Park Kun Young , Kang Soon Ah
Published: June 2021

The protective activity against oxidative stress of extracts from kimchi was investigated under cellular system. Kimchi is the traditional fermented food in Korea, so the extracts from kimchi was prepared by fermentation stage, such as extracts of fresh kimchi (pH 5.8), optimally ripened kimchi (OptR kimchi, pH 4.1), and over ripened kimchi (pH 3.8). Under cellular model of oxidative damage using LLC‐PK1 renal tubular cell, the oxidative damage was induced by 3‐morpholinosydnonimine (SIN‐1). SIN‐1 is a generator of peroxynitrite formed by simultaneously releases of nitric oxide (NO) and superoxide anion, caused cytotoxicity, lipid peroxidation, and NO overproduction in the LLC‐PK1 cells. However, the treatment of kimchi, especially OtpR kimchi, significantly increased the cell viability, inhibited lipid peroxidation and NO formation, as dose‐dependent manner. In addition, overexpression of cyclooxygenase‐2 and inducible NO synthase induced by SIN‐1 were observed, but kimchis down‐regulated the expression levels of both genes. Furthermore, kimchi reduced SIN‐1‐induced nuclear factor kappa B expression and increased inhibitor of kappa B. These results indicate that kimchi, especially OptR kimchi, protect against cellular damage by attenuating oxidative stress induced by ONOO−.
Effects of collagen‐rich Korean traditional foods on the bone metabolism in ovariectomized rats
Authors: Yoon Leena , Jung Ji‐Hye , Kim Hyun‐Sook
Published: June 2021

Postmenopausal women are particularly susceptible to osteoporosis when their production of estrogen declines. In this study, we investigated the effects of collagen‐rich Korean Foods on the bone metabolism in ovariectomized rats. Ten‐week old female Sprague‐Dawley rats were given ovariectomy or sham operation after one week of adaption. After two weeks of recovery periods, rats were given of every other day oral administration of ethanol extract of five different collagen‐rich Korean foods, Samgyetang(SGT), Eogeultang(EGT), Odolpyu(ODP), Jeonyak(JY) and Jokbal(JB) (250 mg/kg BW/day) for 8 weeks. We evaluated daily food intake, body weight gain, uterus and femur weights, serum ALT/AST levels, serum calcium, phosphorus, alkaline phosphatase, creatine, and RANK levels. The serum phosphorus levels were increased in collagen‐rich food groups. And, the RANK level which represents the osteoclast activity showed significant decrease in ODP, JY and JB groups. Considering the significance of halting the activity of osteoclast in postmenopausal women, the frequent consumption of collagen‐rich Korean traditional foods could be desirable to prevent osteoporosis in aging people. This study results could be very meaningful because the actual food samples instead of individual functional component were used in this experiment. Further studies are needed to investigate in depth the various indexes in bone metabolism.
Pigment epithelium‐derived factor ameliorates noise damage to the intra‐strial fluid‐blood barrier
Authors: Shi Xiaorui , Zhang Fei , Neng Lingling , Zhang Jinhui , Jiang Meiyan
Published: June 2021

A unique endothelial‐blood/tissue barrier in the inner ear, termed the “intra‐strial fluid‐blood barrier,” is critical for maintaining cochlear homeostasis. Disruption of the barrier is closely associated with a number of hearing disorders including noise‐induced hearing loss. Noise trauma disrupts the intra‐strial fluidblood barrier leading to lesions, edema and entry of serum proteins. In this report, we identify down‐regulation of pigment epithelium‐derived factor (PEDF) in perivascular resident macrophages (PVM/Ms), a key factor in intra‐strial fluid‐blood barrier hyper‐permeability. Treatment with PEDF substantially protects against deterioration in barrier integrity, a drop in endocochlear potential and hearing loss in noise‐exposed animals. The PEDF treatment protects by promoting expression of tight junction‐associated proteins and stabilizing PVM/Ms by increasing expression of neural cell adhesion molecules. The dramatic effect of PEDF on barrier integrity suggests new strategies for treatment of acoustic stroke. This work was supported by NIH NIDCD DC008888–02A1 (Shi, X.R), NIH NIDCD DC008888–02S1 (Shi, X.R), NIH NIDCD R01‐DC010844 (Shi, X.R), NIH NIDCD R21‐ DC012398–01 (Shi, X.R), NIH P30‐DC005983.
Xeroderma pigmentosum group A protein modulates mitophagy through regulation of mitochondrial‐associated proteins
Authors: Fang Evandro Fei , Scheibye‐Knudsen Morten , Croteau Deborah L. , Bohr Vilhelm A.
Published: June 2021

The Xeroderma pigmentosum group A (XPA) protein plays critical roles in nucleotide excision repair pathway (NER), and patients with XPA deficiency exhibit sun sensitivity, high skin cancer predisposition, and many have progressive neurological disorders. Based on a clinical database that we have established (Scheibye‐Knudsen et al, submitted) we speculated that there might be mitochondrial dysfunction in individuals with XPA. We therefore investigated mitochondrial function in XPA deficient cells, in primary fibroblasts from patients with XPA and compared these to controls and to cell lines complemented with the normal XPA gene. Microarray analysis indicated increased mitochondrial metabolism in XPA deficient cells, and flow cytometry results showed an increase in mitochondrial content. Cellular and mitochondrial reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP) were increased in XPA cells. These cells also had increased numbers of damaged mitochondria and a deficiency in mitophagy after mitochondrial stress. These findings uncover a novel mitochondrial defect in XPA which could be an important factor in the clinical phenotype. We discuss the dysregulation of important mitochondrial proteins in XPA and propose a mechanism.
Effects of Minocycline on Oxycodone‐Induced Responses in Humans
Authors: Mogali Shanthi , Comer Sandra D.
Published: June 2021

Preclinical studies suggest that inhibition of glial activation with minocycline (MINO) modulates opioid‐induced responses while preserving opioid analgesia. This study assessed the effects of minocycline on the abuse liability of oxycodone in humans. Non‐dependent opioid abusers (N=7) participated in this randomized, double‐blind outpatient study. Subjects completed five sessions in which they received 0, 100, or 200 mg MINO with either 0 or 40 mg oxycodone (OXY). Subjective and physiological effects of OXY were measured before and repeatedly after drug administration. Results show MINO did not alter the physiological effects of OXY. Compared to PBO MINO, MINO 200 mg+ OXY 40 mg significantly reduced ratings of “High” (p< 0.05). Both MINO 100 and 200 mg administered in combination with OXY 40 mg significantly reduced ratings of “Good Effect” and delayed the peak rating of “Good Effect” by 60 minutes compared to OXY alone (p<0.05). MINO 100 and 200 mg in combination with OXY 40 mg significantly reduced drug “Liking” compared to OXY alone (p< 0.05). Ratings of drug “liking” of OXY 40 mg when combined with either MINO 100 mg or 200 mg were comparable to PBO OXY. Participants reported that they “Would Pay” significantly less for MINO 200 mg + OXY 40 mg than OXY alone (p<0.001). These results demonstrate that MINO robustly attenuated the positive subjective effects of OXY in recreational opioid abusers.
Tyrosine kinase inhibitors attenuated lipopolysaccharide‐induced acute lung injury during neutropenia recovery in mice
Authors: Lee Hwa Young , Kim In Kyoung , Lee Hye In , Lee Chin Kook , Yeo Chang Dong , Lee Dong Gun , Lee Sang Haak , Kim Jin Woo
Published: June 2021

The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)‐induced ALI during neutropenia recovery in mice. BALB/c mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry (W/D) weight ratio and protein levels in the BAL fluid or lung tissue were determined. Treatment with imatinib or nilotinib significantly attenuated the LPS‐induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor (TNF)‐alpha, interleukin (IL)‐1 beta, IL‐6 and myeloperoxidase (MPO) in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet‐derived growth factor receptor (PDGFR)‐beta and c‐kit in imatinib or nilotinib group were significantly lower than LPS group. Our data indicated that imatinib or nilotinib effectively attenuated LPS‐induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.
Imiqualines: promising anticancer molecules binding colchicine site on tubulin
Authors: Gattacceca Florence , Courbet Alexis , El Messaoudi Safia , Khier Sonia , Constant Caroline , Bec Nicole , Larroque Christian , Pugnière Martine , Doulain Pierre‐Emmanuel , Cuq Pierre , Bonnet Pierre‐Antoine , Masquefa Carine
Published: June 2021

Our group has developed two innovative synthesis strategies that allowed to produce a 50‐member family of Imidazo[1,2a] quinoxaline compounds, named Imiqualines. Based on their strong anticancer potency and anti‐inflammatory properties, Imiqualines have recently been patented in the USA. The aim of the present study was to explore the mechanism of action involved in the cytotoxic effect of the leader Imiqualines, EAPB0203 and EAPB0503. Leader Imiqualines blocked A375 melanoma cells in the M phase of the cell cycle, inhibited purified tubulin polymerization, disrupted tubulin network in A375 and MCF7 cell lines, and bound tubulin on the colchicine binding site, based on in silico and in vitro studies. This finding lead us to test newly synthesized Imiqualines on the in silico model of tubulin. Preliminary results showed a correlation between binding affinity and cytotoxicity, encouraging us to develop this systematic predictive approach to enhance the structure activity relationship knowledge and identify new Imiqualine leaders.

Support GEFLUC, SFPO‐ANP
Effects of manganese tetrakis (4‐N‐methylpyridyl) porphyrin (MnTMPyP) on dexmedetomidine‐induced contractions in the aorta of normal and septic rats
Authors: Manio Michael Magtoto , Vanhoutte Paul M , Man Ricky Y.K. , Ng Jacobus KF
Published: June 2021

Study Objective

The aim of the present study was to investigate the effects of peroxynitrite scavenging on dexmedetomidine‐induced contractions of the rat aorta after acute in vivo exposure to lipopolysaccharide. (LPS)

Methodology

Male SD rats (eight to ten weeks old) were injected intraperitoneally with (1mg/kg) of LPS or normal saline. Two hours later, their aortas were harvested. Aortic rings were suspended for isometric tension recording in organ chambers and incubated with vehicle, L‐NAME (100 uM), indomethacin (10 uM), 1400W (10uM), and the peroxynitrite decomposition catalyst manganese tetrakis (4‐N‐methylpyridyl) porphyrin (MnTMPyP) (10uM). Concentration‐contraction curves to dexmedetomidine (10nM to 10uM) were obtained. Plasma cytokine concentrations were measured before and after the administration of LPS. The expression of iNOS and 3‐nitrotyrosine were measured using immunofluorescence and Western blotting.

Results

LPS treatment attenuated dexmedetomidine‐induced contractions after acute in vivo exposure to LPS and in the presence of MnTMPyP and 1400W, in aortic rings without endothelium. TNF‐á and IL‐6 were increased after 2 hours of LPS.

Conclusion

These data indicate that LPS attenuates the contractile responses to dexmedetomidine and ex vivo treatment with MnTMPyP and 1400W. Circulating endotoxin induces the release of the cytokines TNF‐á and IL‐6 after two hours.
Characterization of different Dexamethasone side effects along time and its possible mechanisms
Authors: Amaral Sandra Lia , Souza Lidiane Moreira , Constantino Paula Bessi , Martuscelli Aline Mio
Published: June 2021

We investigated the time‐dependent side effects of dexamethasone (Dexa) treatment and its possible mechanisms. Forty Wistar rats were treated with Dexa or saline for 1, 3, 5, and 10 days (0.5 mg/kg per day, i.p.). The role of Renin‐Angiotensin System (RAS) was tested using Enalapril treatment (100mg/kg, 10 days). Bodyweight (BW), fasting glucose, food intake, cholesterol (Chol) and tail blood pressure (BP) were measured. Western Blot detected eNOS, VEGF, AMPKα2 and PI3Kinase protein production in tibialis anterior muscle (TA). Food intake decreased from day 1 (−28%) up to day 10 (−35%). BW was significantly reduced after 5 days of treatment (−20%). Glucose increased since the first day (27%, 44%, 64%, 57%, for 1, 3, 5, 10 days, p<0.05). Chol increased since the 1st day and returned to control on day 10. Tail BP was significantly higher on days 3 and 5 (+12%) and returned to basal levels on day 10. Enalapril attenuated the increase of BP induced by Dexa. AMPKα2 but not PI3kinase protein production was significantly reduced (25%) since the first day of drug administration. Dexa down‐regulated VEGF and eNOS protein production from day 5 on. These results suggest that a single dose of Dexa (24h) can alter carbohydrate and lipid metabolism and the mechanism involves CaMKK production and lipolysis. The maintenance of treatment affects hemodynamic, which may be partially mediated by eNOS, VEGF and RAS.

Financial support: FAPESP
Differential Remodeling Characteristics of Femoral and Mesenteric Arteries from Mice with Diet‐Induced Obesity
Authors: Zhao Guiling , Castorena‐Gonzalez Jorge A. , Sowers James R. , Martinez‐Lemus Luis A.
Published: June 2021

Obesity is associated with abnormal vascular responses to vasoactive agents and structural remodeling of vascular walls. We hypothesize that increased vasoconstriction and reduced vasodilation responses in obesity are associated with arterial inward remodeling characterized by reduced passive diameter and increased wall to lumen ratio. We tested this hypothesis in femoral and mesenteric arteries from mice fed normal chow (control) or a high fat and fructose diet for 16 weeks starting at 4 weeks of age. Experiments were performed in pressure myographs with arteries kept at 37C and pressurized to 70 mmHg. Neither femoral nor mesenteric arteries had significantly different responses to phenylephrine, insulin, or sodium nitroprusside between obese and control mice. However, mesenteric arteries from obese mice had reduced wall to lumen ratios compared to controls (0.11 ± 0.002 vs. 0.13 ± 0.003, respectively). This reduction in media to lumen ratio was associated with a reduced cross‐sectional area of the arterial wall, reduced distensibility and an increased Young's modulus of elasticity. In comparison, no changes in media to lumen ratio were observed in femoral arteries. These results suggest that structural changes in the mesenteric arterial tree occur in the absence of functional abnormalities and independent of remodeling in other vascular beds. (Supported by NIH HL‐088105 to LAM)
Silver nanoparticles induces heat shock response and provides an anti‐inflammatory effect in Clone 9 cells
Authors: Ho Chia‐Ching , Huang Li‐Ju , Yang Rei‐Cheng
Published: June 2021

Silver nanoparticles (Ag‐np) are currently emerging as one of the fastest growing product categories in the nanotechnology industry with focus on antimicrobial activity. In recent studies, in addition to the antimicrobial activity, it had been proved that silver nanoparticles has cytotoxicity in primary liver cells and increase both superoxide dismutase and glutathione. Silver nanoparticles have also been found to cause mitochondrial damage and induced ROS, oxidative stress, apoptosis and the expression of heat shock protein70 (Hsp70). In this study, we aimed to explore the potential role of Ag‐np‐induced Hsp70 in protecting the cell death damaged by TNF‐alpha. The results showed that clone 9 cells, a hepatic epithelial cell line, have an optimal over‐expression of Hsp70.upon exposure to 100 μM of Ag‐np for 8 hours, without evidence of changes in the survival rate by MTT assay. After Ag‐np pretreatment, TNF‐α was added as a cell death inducer to observe the protection of Hsp70. The protective effect was confirmed by the significantly increased survival rate in Ag‐np pretreated clone 9 cells. It was concluded that optimal dose of Ag‐np induced Hsp70 over‐expression and exerted its protective function against proinflammatory cytokine‐induced cell death. These results highlight the therapeutic potential of Ag‐np in inflammatory diseases.
Estradiol Enhances Hyaluronic Acid Secretion from Vaginal Epithelial Cells
Authors: Kitchel Alyssa , Teat Stephanie , Woodard‐Grice Alencia
Published: June 2021

Hyaluronic acid (HA) is a relatively simple structured glycosaminoglycan that is an important hydrating component of the extracellular matrix. Previous literature suggests estradiol (E2) inhibits the secretion of HA in vascular smooth muscle cells (VSMCs) by reducing the levels of hyaluronic acid synthase‐1 (HAS1). However, this relationship has not been investigated in vaginal tissues, which are considerably more hydrated when estrogen is present. We hypothesize that E2 increases the secretion of HA in vaginal epithelial cell cultures. To examine this relationship, vaginal epithelial cells (VK2) were synchronized by serum withdrawal and subsequently stimulated with varying concentrations of E2 for 6 and 24 hours. Following treatment, gene expression of three HAS isoforms was analyzed via qPCR and protein secretion of HA was assessed by ELISA. After 6 and 24 hours, gene expression of HAS1 was decreased with 100 nM E2 (0.309, 0.345 fold respectively) compared to no E2 (p<0.05). Unlike VMSCs, with 100nM of E2 stimulation, HA protein secretion was increased at 6 hours (79.19 pg HA/μg total protein) compared to 0nM and 10nM (p<.007) and 24hrs (228.8 pg HA/μg total protein) compared to all other E2 treatments (p<0.05). These results suggest that estrogen‐dependent regulation of HA in VK2 cells involves a change in HA secretion, not synthesis, in order to maintain a hydrated extracellular matrix.
Clickable gamma‐secretase modulator photoaffinity probes bind distinct sites on presenilin
Authors: Murrey Heather Elizabeth , Pozdnyakov Nikolay , Crump Christina J , Pettersson Martin , Li Yue‐Ming , Bales Kelly R , Johnson Douglas S
Published: June 2021

γ‐Secretase is an intramembrane aspartyl protease that cleaves the amyloid precursor protein to generate Aβ species, including the neurotoxic Aβ‐42. Aβ‐42 is a component of β‐amyloid plaques, and is believed to play a causative role in Alzheimer's disease (AD). γ‐Secretase modulators (GSMs) have emerged as a potential treatment for AD because they decrease the production of Aβ‐42 without affecting the processing of other critical γ‐secretase substrates. We used clickable GSM photoaffinity probes to identify the protein target of different classes of GSMs and to probe their mechanism‐of‐action. Probes (i.e., E2012‐BPyne and GSM‐5) were synthesized with a benzophenone or aryl azide for photocrosslinking the compound to the target proteins and an alkyne handle for click chemistry. Cell membranes or live cells were treated with the GSM probe with or without competitor compounds from various GSM and γ‐secretase inhibitor (GSI) classes. Samples were UV‐irradiated followed by click chemistry with biotin‐azide, enriched on Streptavidin and detected by Western blotting. These studies revealed distinct allosteric binding sites on the N‐terminal fragment of presenilin 1 (PS1‐NTF). Furthermore, E2012‐BPyne labeling of PS1‐NTF was potentiated by the presence of the active site‐directed GSI, L458, suggesting a degree of cooperativity between the protein's active site and modulatory binding sites of certain GSMs.
Fos expression on medullary and hypothalamic areas after resistance exercise in rats.
Authors: Santana Michael N , Macedo Fabricio N , Melo Vitor U , Oliveira Larissa R , dos Santos Robervan V , Junior Waldecy L , dos Santos Marcio R Viana , de Santana‐Filho Valter J
Published: June 2021

The acute effects of exercise are generated by alterations in the autonomic nervous system that is mediated through the integration of multiple nuclei of autonomic control. The aim of this study was to evaluate the Fos protein expression on the hypothalamic and medullary areas of cardiovascular control after a single bout of resistance exercise (RE). Were used Wistar rats (250g–300g) divided into two groups: sham (SH) and resistance exercise (RE). The animals performed the RE protocol (10 sets of 10 repetitions with 2 min for recovery) in a squat apparatus with 60% of 1RM. The animals were anesthetized, perfused, the brain was removed and sliced in a cryostat for immunohistochemistry method. The brain sections were subjected to immunofluorescence protocol. Fos protein immunoreactivity increase when compared to SH in the nucleus tractus solitary (RE = 15.3 ± 0.6 vs. SH = 1.6 ± 0.6), in the caudal ventrolateral region of the medulla (RE = 23.3 ± 0.8 vs SH 1.3 ± 0.3) and in the paraventricular nucleus of the hypothalamus (RE = 59.3 ± 4.2 vs SH 1.3 ± 0.3), we showed that after RE there is an intense activation of important brain areas for cardiovascular control during the post exercise period. Suggesting mobilization and possible interaction of specifics nuclei of brain to correct homeostatic changes produced by RE. Research support: CAPES, Fapitec.