bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Inhibitor of the Histone Acetyl Transferase Activity of p300/CBP Associated Factor (PCAF)
Authors: Modak Rahul , Basha Jeelan , Kundu Tapas 
Published: June 2021

We have identified a natural compound from an Indian traditional medicinal plant which is being used to treat fever, inflammatory diseases, and a variety of gastrointestinal ailments for thousands of years. The compound (MJTK‐1) has been shown to have antifertility, anthelmintic, antipyretic, analgesic, antiinflammatory and antibacterial activities. Here we report that MJTK‐1 inhibits lysine acetyl transferase (KAT) activity of Tip60, hGCN5, p300 and PCAF in vitro. MJTK‐1 specifically inhibits PCAF (KAT3B) up to 10μM concentration with Ki =1.2 ±0.5 μM. MJTK‐1 does not inhibit methyltransferases CARM‐1 and G9A. 25μM MJTK‐1 treated HEK 293T cells show specific down regulation of histone H3K9 acetylation without any alteration of other histone acetylation marks. Immunohistochemical and western blot analysis of liver tissues from MJTK‐1 treated mice showed specific down regulation of histone H3K9 acetylation. Presumably, MJTK‐1 at least with a great preference inhibits the HAT/ KAT activity of PCAF in vivo. Presently we are analysing the mechanism of this specificity as well as its biological implication in the context of epigenetics.This work is supported by Indian Council for Agricultural Research and Jawaharlal Nehru Centre for Advanced Scientific Research, India.
Novel Cyclic Peptoid Ligands Targeting Oncoprotein Prothymosin α
Authors: Qi Xin , Kodadek Thomas 
Published: June 2021

There is great interest in the discovery of synthetic molecules that recognize proteins with high specificity and affinity. Many cyclic peptide and depsipeptides have been found to display potent biological activities and often have better pharmacokinetic properties than their linear counterparts. We have applied a dual‐methionine strategy to incorporate a peptoid library into a cyclic scaffold to identify peptoid ligands targeting oncoprotein Prothymosin α that modulates apoptosis. To facilitate our screening effort, TentaGel beads that have bound the His‐ProT α were retained by the magnet through a peptoid—protein·anti‐His antibody·secondary antibody—Dynabead bridging interaction. We identified lead compounds that bind oncoprotein ProT α with moderate affinity. Furthermore, the microarray results confirmed that our cyclic peptoid hits target ProT with high specificity. In summary, we prepared a series of cyclic peptoid library and evaluated their potency for binding oncoprotein ProT. In particular, we demonstrated the advancement of using magnetic separation to accelerate the screening process and our approach allows more powerful selection of peptoid libraries.This work was supported by the National Institutes of Health (1 P01‐DK58398).
Conformational analysis and design of disulfides in antiparallel β‐sheets and helices
Authors: Santhanagopalan Indu , Kumar Senthil , Thakurela Sudhir , Gupta Mansi , Bhaskara Ramachandra , Kochat Veena , Ramakrishnan Chandrasekharan , Varadarajan Raghavan 
Published: June 2021

A nonredundant data set having 5025 polypeptides with 2311 disulfides was used to study cross‐strand disulfides (CSDs) in antiparallel beta‐sheets, and intrahelical disulfides (IHDs).75 and 1 CSDs were found at non‐hydrogen‐bonded (NHB) and hydrogen‐bonded (HB) registered pairs, respectively. Disulfides at HB pairs lead to steric repulsions with main chain and require a rare, positive χ1 value for at least one of the Cys. 13 disulfides were introduced in NHB and HB pairs in 4 model proteins: Leu binding protein (LBP), Leu, Ile, Val binding protein (LIVBP), maltose binding protein (MBP), and Top7. The LIVBP mutant did not show disulfide formation. Relative to wild type, LBP and MBP mutants were destabilized with respect to chemical denaturation, although the exposed NHB LBP mutant showed an increase of 3.1 °C in Tm. Both exposed and 2 of the 3 buried NHB Top7 mutants were stabilized. All 4 HB Top7 mutants were destabilized (ΔΔGo = −3.3 to −6.7 kcal/mol). Thus, CSDs engineered at exposed NHB pairs can be used to improve protein stability.35 examples were found of IHDs between the N‐Cap and 3rd helical positions. Cys pairs were introduced at N‐Cap‐3; 1,4; 7,10 in 2 helices of an E. coli thioredoxin (Trx) mutant. Disulfides spontaneously formed only at positions N‐Cap‐3 during purification. All oxidized and reduced mutants were destabilized relative to nSS Trx. All mutants were mildly redox active.
Supplement Moringa oleifera leaves and their impact on the nutritional status of vitamin A, iron and zinc in preschools: A pilot study
Authors: grijalva maria isabel , Fernandez Isaura Victoria , Ponce Jose Antonio , Artalejo Elizabeth , nieblas amparo , Gonzalez Luis Enrique 
Published: June 2021

ObjectiveTo evaluate the effect of a dried leaves of Moringa oleifera(MOL) supplement, on the prevalence of vitamin A deficiency(VAD), and iron and zinc status in preschool children at risk of malnutrition in rural disadvantaged areas of Hermosillo, Mexico.Subjects and MethodsA quasi‐experimental intervention accomplished a clinical study itself (n=56 children aged 3–5 years). A group (n=31) was supplemented with 1.17 g/day of MOL during 5 months, and another with no supplementation (n=25). Biochemical indicators (serum retinol and zinc, protoporphyrin, and hemoglobin) before and after supplementation. Socioeconomic, dietary and parasitic factors were used as covariate.ResultsPreschool children of farm workers in poverty communities showed inadequate dietary pattern of vitamin A (66.7%), iron (50.6%) and zinc (27.1%). There was a high prevalence of VAD (43.8%), anemia (11.9%) and intestinal parasites(from 47% to 64%). At the end of the study, supplementation reduced the prevalence of VAD (p<0.05) from 40% to14.3% in the supplemented group. Significant changes for hemoglobin concentration between groups was observed (p<0.001).ConclusionMOL supplementation showed a protective effect to maintain adequate levels of hemoglobin in the study population.
Novel gene fad104 is required for lung morphogenesis
Authors: Kishimoto Keishi , Nishizuka Makoto , Osada Shigehiro , Imagawa Masayoshi , Imagawa Masayoshi 
Published: June 2021

Previously, we identified fad104 (factor for adipocyte differentiation 104) as a novel gene whose expression was induced in the early stage of adipogenesis. Mouse fad104 encodes a 132‐kDa protein, which contains nine fibronectin type III domains and a transmembrane region. We have reported that fad104 promotes adipogenesis and that deletion of fad104 causes neonatal death. However, the cause of death in fad104‐deficient mice is unclear. Here, we attempted to clarify the cause of death in fad104‐deficient mice, and uncover the physiological role of fad104.□@ First, phenotypic and morphological analyses showed that fad104‐deficient pups displayed cyanosis and died from respiratory distress immediately after birth. In addition, fad104‐deficient lungs were small and its alveolar spaces were not dilated adequately. Furthermore, we revealed that FAD104 was expressed in alveolar epithelial type II (ATII) cells in the developing lungs. Moreover, the ATII cells in fad104‐deficient lungs were immature and attenuated the expression of surfactant‐associated proteins.In conclusion, this work demonstrated that fad104 has a crucial role in lung morphogenesis at least in part by regulating ATII cell maturation.
Total vitamin D intake and predictors of circulating 25(OH)D in african american men
Authors: Agurs‐Collins Tanya , Dodd Kevin , Williams Erica , Kittles Rick 
Published: June 2021

PurposeEvidence suggests that low vitamin D status is associated with chronic disease including colorectal cancer risk and all‐cause mortality. The purpose of this study was to assess vitamin D status against the new Institute of Medicine (IOM) vitamin D recommendation and to identify predictors of circulating 25(OH)D in 287 healthy African American men.MethodsTotal vitamin D intake and lifetime ultraviolet light (UV) exposure were measured by questionnaires. Circulating 25(OH)D was measured using serum. Descriptive statistics and linear regression models were used to assess vitamin D intake and explore predictors of circulating 25(OH)D.ResultsMean total vitamin D intake (food and supplement) was 272.3 IUs/day (95% CI:245.0,299.6), with only 10% of the sample meeting the 600 IUs recommendation. Mean circulating 25(OH)D was 18.0 ng/ml (95% CI:17.0,19.1), with 35% of the sample who met the recommended 20 ng/ml. A significant predictor of 25(OH)D was total vitamin D intake (food and supplement) p<0.001; lifetime UV exposure was suggestive (p=0.08). We estimated that an increase of 200 IUs from total vitamin D (food and supplement) would increase circulating levels of 25(OH)D by 1.4 ng/ml.ConclusionsWhen compared to the IOM recommendation, circulating vitamin D and intakes were inadequate, which may partially explain increased cancer risk and mortality among African American men.
White potatoes, non‐fried, do not displace other vegetables in meals consumed by American children and adolescents aged 4–18 years
Authors: Drewnowski Adam , Rehm Colin D , Beals Katherine 
Published: June 2021

White potatoes are an accepted, affordable, and nutrient‐rich food. However, there are concerns that potatoes may displace other vegetables from meals and diets of American children. Using data from 4‐cycles (2001–08) of the National Health and Nutrition Examination Survey (NHANES), we evaluated whether consumption of white potatoes, baked, roasted, or boiled, displaced other vegetables from the meals of children and adolescents aged 4–18 y. Approximately 10,600 lunches and 11,500 dinners were characterized by place (at‐home or away from home) and by source of food (e.g., store or school cafeteria). Children and adolescents consuming white potatoes, baked, roasted, or boiled were identified using the individual‐food record. The median, inter‐quartile range and survey‐weighted mean number of other vegetable servings per 1000 calories were estimated for each meal. Children whose weekday lunches included non‐fried white potatoes consumed a median of 0.37 servings of other vegetables at lunch as compared to only 0.19 servings for children whose lunches did not include potatoes. There was no evidence that white potatoes, non fried, displaced other vegetables in school lunches. Meals containing potatoes had significantly higher amounts of vitamin C, potassium and fiber per 1000 calories than meals that did not contain potatoes. In some contexts, white potatoes, non‐fried, may be an indicator of a more nutrient‐dense and healthful meal. Supported by the US Potato Board.Society: American Society for NutritionAbstract ID: 9123
Adherence to Mediterranean Diet and Counseling in Arterial Hypertension
Authors: Trovato Guglielmo M. , Martines G.Fabio , Trovato Francesca M , Pirri Clara , Pennisi Alessia , Pace Patrizia , Catalano Daniela 
Published: June 2021

Nutritional guidelines in Arterial Hypertension (AH) are presently not sufficiently followed in Italy as elsewhere. Dietary adherence of patients can be a consequence of the different health professionals involved. Adherence to Mediterranean Diet and its Score (AMDS; range 0–55) is a tool used as a proxy for suggested guidelines in Italy.Methods630 AH out‐patients (F 334, M 296, age 61,9±11,9 years, BMI 27,8±5,4 Kg/m2 ) were studied. A dietary history, with 7‐days food recall records by Dietosystem Software, and AMDS were assessed.AH as a cardiovascular risk factor was explained to patients and dietary treatment prescribed. Difference between one year dietary changes were assessed comparing counseling results of Primary M.D.s, Specialist M.D.s (Cardiologist) and dietitians.ResultsSignificant one‐year AMDS changes were observed in each group.Greater AMDS change is observed in Dietitians' group: AMDS change from 27,60±8,77 to 37,20±4,52 (p < 0.0001).Significant BMI changes are present in Primary M.D.s group (BMI from 28,35±4,43 to 26,75±3,18; p<0.0001) and in Dietitian counseling group (BMI from 30,22±6,75 to 26,72±4,87;p<0.0001).ConclusionThe need of a consistent professional counseling in AH is necessary due to the co‐existence of obesity and of the low adherence to suggested dietary guidelines.Beneficial changes can be achieved using Mediterranean Diet as a nutritional and friendly paradigm.
TOTAL ANTIOXIDANT CAPACITY, LIPID PEROXIDATION, BIOCHEMICAL PARAMETERS AND BLOOD PRESSURE IN GENETICALLY OBESE RATS
Authors: Pierine Damiana Tortolero , de Faria Jacob Mirelle , Ortega Tainá Teixeira , Braz Mariana Gobbo , Campos Dijon Henrique Salomé , Cicogna Antonio Carlos , Corrêa Camila Renata , Ferreira Ana Lúcia dos Anjos 
Published: June 2021

Obesity is a disease that is associated with increased risk of mortality. Genetically obese Zucker rats (mutation of the leptin receptor gene, fa/fa) have been used as an experimental model for the study of obesity. These rats seems to display a sufficient line of defense against oxidative stress during the development of obesity. The aim of this study was to evaluated the total antioxidant capacity, lipid peroxidation, biochemical parameters and blood pressure in obese Zucker rats (ZO) males at 34 weeks of age. Ten Zucker rats (ZO, n=5, control n=5) were used in the study. Body fat (g), Total antioxidant performance (TAP: %), malondialdehyde (MDA: μM), glucose (mg/dL), triglycerides (mg/dL), total cholesterol (TC, mg/dL), and systolic blood pressure (SBP: mmHg) were analyzed. Compared to the control group, ZO showed increased (p <0.05) in body fat (89.5±11.77 vs 16.8±2,42), glucose (180.2±35.9 vs 111.3±11.3), triglycerides (260.5±143.4 vs 40.3±12.7), TC (85.1±40.9 vs 40.3±12.7) and SBP (155.4±7.2 vs 128.0±8.0). The groups showed similar values (p>0.05) of TAP (44.1±19.5 vs 59.6±14.3) and MDA (0.21±0.02 vs 0.19±0.02). These data support the conclusion that obese Zucker rats at 34 weeks of age not show losses of antioxidant defense system, despite the comorbidity installed, such as hyperglycemia, dyslipidemia and hypertension.Financial Support: CAPES, FAPESP
MEDITERRANEAN DIET ADHERENCE. WHICH RELATIONSHIP WITH OBESITY AND INSULIN RESISTANCE
Authors: Trovato Guglielmo M. , Catalano Daniela , Pirri Clara , Trovato Francesca M , Pennisi Alessia , Puglisi Claudia , Martines G. Fabio 
Published: June 2021

Relationship of Adherence to Mediterranean Diet, insulin sensitivity and obesity is controversial. Adherence to this dietary profile was associated with reduced weight gain, so that this dietary pattern could be recommended to slow down age‐related weight gain, but others report increased Insulin Resistance (IR).Methods187 consecutive non‐diabetic overweight‐obese patients (F 114, M 73, years 47,17±13,95, BMI 32,72±5,79), no/low alcohol habits (< 20 ml/day), were referred to our Day‐Hospital‐Clinic for dietary counseling. Insulin Resistance by HOMA (Homeostasis‐Model‐Assessment‐IR) and the Adherence Mediterranean Diet Score (AMDS: range: 0–55) were assessed. Dietary data were collected by monthly dietary recall; Dietosystem® diet prescriptions were provided.ResultsNo correlation between AMDS vs. BMI (r= −0,028; p: NS ) whereas inverse correlation between AMDS and HOMA (r= −0,306; p: <0,0001) were found. By Odds Ratio the risk for IR (HOMA≥1.7) is increased by more severe obesity (OR: 3,002; CI 1,509–5,972) and decreased by 75% by greater AMDS (OR: 0,266; CI: 0,136–0,523). Multiple Linear Regression model (p< 0,0001) explains by AMDS, BMI and HDL 25,7 % of variance to HOMA.ConclusionMediterranean Diet Adherence in obesity is associated with lower prevalence and severity of IR, despite the association with greater BMI. This dietary pattern might be advised for improving insulin sensitivity.
Olmesartan reduces angiotensin II without affecting ACE activity in kidneys of mRen2.Lewis rats
Authors: Varagic Jasmina , Ahmad Sarfaraz , Moniwa Norihito , Brosnihan K. Bridget , Ferrario Carlos Maria 
Published: June 2021

We investigated the possibility that the antihypertensive actions of the angiotensin II (Ang II) receptor blocker –olmesartan medoxomil– may in part be associated with a functional inhibition of angiotensin converting enzyme (ACE) activity due to increased Ang‐(1–7) production in the absence of changes in plasma Ang II (Ichikawa, 2001; Agata, 2006). Experiments were performed in 10 – 11 week old mRen2.Lewis congenic hypertensive rats administered either a saline vehicle (VEH, n=7) or olmesartan (OLM: 0.5 mg/kg/day for 6 weeks; n=7) by subcutaneous implantation of osmotic minipumps. Plasma and kidney tissue Ang peptides and serum and kidney ACE activity were measured at the completion of the experiments.

VEH
OLM

SAP (mm Hg)
208 ± 3
99 ± 3*

Kidney cortex

Ang peptides (fmol/mg)

Ang I
7.6 ± 0.9
16.7±2.2*

Ang II
15.9±1.6
6.3±0.6*

Ang‐(1–7)
10.3±1.6
7.71±1.5

ACE activity (nmol/mg/min)
1.9±0.7
2.4±0.9

Plasma/Serum

Ang peptides (fmol/ml)

Ang I
92±6
565 ± 77*

Ang II
31±5
254 ± 43*

Ang‐(1–7)
27±4
60 ± 5*

ACE activity (nmol/ml/min)
69±5
77 ± 1

SAP= Systolic Arterial Pressure;
p<0.05

Our results support the concept that the reduction in Ang II kidney content may contribute to the protective effects of olmesartan on renal structure and function. We also provide evidence for independent regulation of Ang II between plasma and kidney tissue in response to AT1 blockade. The absence of changes in ACE activity suggests no measurable effect of olmesartan on ACE activity. This work is supported by an unrestricted grant from Daiichi Sankyo, Inc.
Ferrets ‐ a small animal alternative to dogs in cardiovascular pharmacology studies
Authors: Main Bradley W , Hunter Randy , Adams Stephanie , Doyle Jennifer , Clawson Christine , Gould Kenneth 
Published: June 2021

Ferret cardiac ion channels are similar to those in human, dog and to those in species used for in vitro cardiac electrophysiology studies. The ferret heart is relatively large making it suitable for instrumentation while their overall small size (approximately 900g) allows for reduced compound use. The ferret can be a suitable alternative to the dog for early screening of compounds with potential cardiovascular effects. Recent technology improvements in small animal telemetry allow the acquisition of two pressure signals in a single animal. We implanted HD‐S21† pressure transmitters into ferrets and recorded arterial and left ventricular pressures and ECGs in response to milrinone.Dose responsive increases were observed in left ventricular function including indices of inotropy, lusitropy and heart rate. Systemic arterial blood pressure decreased at 3 and 10 mg/kg of milrinone.

Milrinone Dose
Systolic Pressure* (mmHg)
LV Heart Rate* (beats/min)
dP/dtmax * (mmHg/sec)
dP/dtmin * (mmHg/sec)

1 mg/kg
no change
↑ 51.7 ± 16.2
↑ 6953 ± 1693
↑ 1419 ± 987

3 mg/kg
↓ 23.6 ± 4.8
↑ 92.0 ± 14.7
↑ 8011 ± 1212
↑ 1840 ± 563

10 mg/kg
↓ 26.1 ± 4.9
↑ 114.2 ± 9.7
↑ 8490 ± 661
↑ 2006 ± 880

Change from vehicle‐treated group

In summary, data with a high degree of fidelity and reproducibility can be obtained in a small animal species like the ferret. This species can be used as an alternative to the dog in cardiovascular pharmacology studies.
The Cost Effectiveness of Topical Minoxidil Therapy in Management of Baldness
Authors: Raja Dewan Saiful , Sultana Bahar 
Published: June 2021

“Use it or loss it (Rogaine),” is an advertisement as a cure for baldness. Rogaine is a commercial name for Minoxidil. Minoxidil is a vasodilator used orally for treatment of severe to malignant hypertension. Minoxidil therapy also causes hypertrichosis (increase of body hair). This drug is used topically to treat baldness.Minoxidil is not effective in halting the receding hairline on the frontal scalp. Its antibald effect is limited to the vertex of the head. It takes several months (2–4) to regrow hair by twice‐a‐day application. Continuous use of Minoxidil topical solution is needed to maintain hair regrowth. Stopping Minoxidil application causes loss of newly regrown hair in 3 to 4 months.Purpose of this case study will answer several questions. Is Minoxidil effective against baldness? Is it a permanent, cost‐effective remedy for baldness? What age group will get the maximum benefit from Minoxidil therapy? What types of baldness are amenable to Minoxidil therapy? Is it effective in female baldness? Is Rogaine free from remarkable adverse effects? What are the causes of baldness? Is there any permanent remedy for baldness?
In vitro characterization of a dual‐receptor targeted drug delivery system for treating vascular diseases
Authors: Lamberti Giuseppina , Wu Fan , Kiani Mohammad F. , Wang Bin 
Published: June 2021

IntroductionDrug delivery systems targeted to the vasculature provide an effective mean for increasing the therapeutic efficacy of various drugs. In this study we present a novel dual‐receptor (selectins and ICAMs) targeting approach to enhance the drug carrier's binding efficiency to the inflamed tissue in vascular diseases.MethodsFlorescent microspheres were prepared by coating the surface with different ratios of antibodies against ICAM‐1 (aICAM‐1) and E‐selectin (aE‐selectin). A flow chamber was used to study the interaction of the microspheres with TNF‐α activated HUVEC under different shear flow conditions.ResultsMicrospheres coated with 2:1 ratio of aICAM‐1 and aE‐selectin had the highest binding efficacy compared to the single antibody coated microspheres. The number of aICAM‐1+aE‐selectin microspheres bound to HUVECs appeared to decrease with increase in wall shear stress in the flow chamber. Moreover, the number of adherent aICAM‐1+aE‐selectin microspheres was significantly higher than the adherent aE‐selectin microspheres under different flow conditions.ConclusionsWe conclude that the adhesion efficiency of the two‐receptor targeting microspheres is significantly higher than the single‐ligand microspheres under various flow conditions and that the drug carrier adhesion ability can be optimized by optimizing the ratio of the two ligands on the surface of the microsphere.
Vascular Endothelial Dysfunction with Age is Related to Increased Sympathetic Nervous System Activity in Women, but Not Men
Authors: Kaplon Rachelle Elizabeth , Walker Ashley Elizabeth , Seals Douglas R 
Published: June 2021

We tested the hypothesis that vascular endothelial dysfunction (impaired endothelium‐dependent dilation, EDD) with aging is related to increases in sympathetic nervous system (SNS) activity. In 314 healthy adults aged 18 to 79 years, age was inversely related to EDD (brachial artery flow‐mediated dilation, FMD) (r=−0.30, P<0.001) and positively related to plasma norepinephrine concentrations (PNE) (r=0.49, P<0.001). Brachial FMD was inversely related to PNE in the overall group (r=−0.25, P<0.001), as well as in men only (n=187) and women only (n=127). After controlling for age (multiple regression analysis), brachial FMD remained related to PNE in women (r=−0.24, P<0.01), but not men (r=−0.03, P=0.68). PNE independently predicted FMD in women after further adjustment for conventional risk factors for cardiovascular disease. Indeed, PNE was the strongest independent predictor of FMD in women (r=−0.25, P<0.01). Endothelium‐independent dilation (EID, sublingual nitroglycerin), a measure of vascular smooth muscle sensitivity to nitric oxide, was positively related to PNE in men (P<0.05), but not women (P=0.49). EID did not account for the lack of an independent relation between FMD and PNE in men. These findings suggest that increased SNS activity may play an important role in modulating EDD with aging in women, but not men.Supported by NIH AG013038, AG015897, AG031617, AG00279, RR025780, AHA 0715735Z