bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of autophagy in erlotinib‐resistant lung cancer and the synergistic induction of cell death with combination cisplatin and erlotinib treatment by Atg3 modulation
Authors: Lee Jasmine G , Wu Reen 
Published: June 2021

ObjectiveErlotinib resistance (ER) in non‐small cell lung cancer (NSCLC) is a major problem clinically. Therefore, in this study we tested whether combination of low dose erlotinib and cisplatin is effective against ER and specifically examined the role of autophagy in ER.MethodsPC9 cells were used to establish erlotinib resistant cells (PC9ER). Cell survival was quantified with Alamar blue assay. LC3II and regulatory proteins of autophagy were measured by western blot. SiRNA was used to modulate protein translation.ResultsCombination of low dose erlotinib‐cisplatin induced synergistic cell death in PC9ER cells and this response was related to a decrease in autophagy. Concordantly, rapamycin increased ER and 3‐MA sensitized cell death response in PC9ER cells. Western blot analysis of autophagy regulatory proteins showed significantly higher baseline levels of LC3II and Atg3 in ER cells as compared to the sensitive PC9 and a significant decrease in Atg3 level was seen with combination treatment. Atg3 SiRNA transfection resulted in the reversal of the resistance in PC9ER cells to both erlotinib‐alone and combination treatment.ConclusionsOur data suggests that ER lung cancer cells are responsive to combined low dose erlotinib‐cisplatin treatment by targeting the baseline over production of Atg3 and that Atg3 is a key regulator/promoter of ER in NSCLC.This research was supported by NIH‐T32 grant.
The role of G0/G1 switch gene 2 in mitotic clonal expansion during adipogenesis
Authors: Choi Hyeonjin , Lee Hye-Min , Kim Hyo Jung , Kim Jae-woo 
Published: June 2021

One of the earliest events occurring in adipogenesis is mitotic clonal expansion which is required for differentiation of 3T3‐L1 cells. In this study, we carried out microarray analysis and analyzed genes which might play an important role during this process. Among them, we sorted out candidates, G0/G1 switch gene 2 (G0S2) which is highly expressed in brown and white adipose tissue and is greatly up‐regulated during mouse 3T3‐L1 adipogenesis. When knockdown of endogenous G0S2 inhibits differentiation and decreases the expression of adipocyte specific genes. Moreover, its knockdown induced apoptosis. G0S 2 is a novel putative target gene of PPAR¥ã. PPAR¥ã, which is most highly expressed in adipose tissue, is known as the master regulator of adipogenesis. The absence of PPAR¥ã in 3T3‐L1 fibroblasts by RNA‐mediated interference knockdown impaired adipocyte differentiation same as knockdown of G0S2. And its knockdown caused apoptosis in 3T3‐L1 preadipocytes. These results show that G0S2 is an important role for differentiation of 3T3‐L1 preadipocytes into adipocytes.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011‐0030711 and 2011‐0015665) and by Korean Research WCU grant (R31‐2008‐000‐10086‐0) from the Korean Ministry of Education, Science, and Technology.
The Effect of the Lipid Environment on Drug Binding and Transport by the P‐Glycoprotein Multidrug Transporter
Authors: Sharom Frances Jane , Clay Adam T. 
Published: June 2021

The P‐glycoprotein multidrug transporter (Pgp, ABCB1) is an ABC protein that effluxes hundreds of structurally unrelated compounds from cells, and is implicated in multidrug resistance in many human cancers. The membrane environment is critically important for Pgp function since lipophilic substrates partition into, and are pumped out of, the membrane. Using purified Pgp reconstituted into proteoliposomes of defined lipids, the effect of the bilayer melting transition on the lipid partition coefficient, binding affinity, and initial rate of transport was measured for Hoechst 33342, LDS‐751 and MK‐571. All drugs partitioned best into liquid crystalline lipid, and bound to Pgp with millimolar affinities within the membrane, suggesting that they interact with the protein weakly. Pgp drug binding affinity was modulated by both the lipid phase state and acyl chain length, and was higher for all drugs in the rigid gel phase. The kcat values for Pgp‐mediated drug transport were also sensitive to lipid melting, however, they were higher in the liquid crystalline phase. Transition state analysis showed the existence of entropy‐enthalpy compensation and an isokinetic relationship between ΔH‡ and ΔS‡. The transport rate is proposed to be controlled by the drug binding affinity and a large conformational change, rather than the rate of ATP hydrolysis.This research is funded by the Canadian Cancer Society (grant #700248).
Identification of environmental supports for healthy eating in older adults
Authors: Sylvie Amanda , Cohen Nancy L 
Published: June 2021

The nutritional status of older adults (OA) correlates to their quality of life, ability to live independently, and risk for developing costly chronic illnesses. An OA's nutritional wellbeing can be impacted by multiple socio‐environmental factors including access to healthy and affordable foods, congregate meal sites, and nutritious selections at restaurants. Research related to improving the nutritional status of OA through environmental changes is limited. The objective of this study was to identify priority areas within a community's environment to enable healthier food choices in OA.Twelve experts in aging and nutrition participated in an online brainstorming session (as two panels of six experts). Transcripts were analyzed to determine primary factors that enable healthy eating in OA, and behavioral settings that are changeable and would impact OA nutrition. Major enablers identified were accessibility, affordability, social support, and living accommodations. The panels identified critical behavioral settings as food stores, restaurants, religious settings, congregate nutrition sites, senior housing, and health care settings. The enablers and behavioral settings will be prioritized based on their contributions to the goal of improving OA nutrition using the Analytic Hierarchy Process. Priority ratings and implications for community public health planning will be discussed.Grant Funding Source: USDA/NIFA NE 1039
A study on the nutritional status and effect of iron and calcium intervention in Korean preschool children
Authors: Shin Kyung Ok , Jung Tae Hwan , Hwang Hyo Jeong , Choi Kyung Soon , Park Hyun Suh , Chung Keun Hee 
Published: June 2021

In a previous study, the Fe, Ca, Zn, niacin contents of preschool children were found to be deficient. Therefore, in this study, Fe and Ca were supplied through 4 different diet types: A, B, C, and D (A : Fe 0.63mg, Ca 27.5mg, B : Fe 15mg, Ca 232mg, C : Fe 30mg, Ca 232mg, and D : Fe 15mg, Ca 462mg). In total, 135 childrenˈs blood samples were analyzed in order to determine anemia status. Ferritin levels increased significantly in the group fed B, C, and D (Fe and Ca supplemented) but not in group A (p<0.05). Children with ferritin levels less than 20 ng/ml before intervention showed a significant increase after intervention, and ferritin levels significantly increased in the group supplied Fe 30mg and Ca 232mg (C group). Ferritin levels decreased in children with ferritin levels higher than 30 ng/ml before intervention. Therefore, intervention was not necessary for children whose ferritin levels were high enough before intervention. Children with Hb levels less than 12g/dl showed a significant decrease, but children who were supplemented with 30mg of Fe did not show a significantly higher level of Hb than those supplemented with 15mg of Fe. The value of Fe saturation(%) was significantly increased by 15.2% in children with transferrin Fe saturation(%)<20% after intervention of Fe 15mg & Ca 232mg, but the saturation of Fe was rather decreased by the intervention of Fe 30mg & Ca 232 mg or Fe 15 mg & Ca 464mg(C and D groups). The mean value of TIBC was in the normal range after intervention, and there was no significant difference among the groups. Therefore, Fe intervention increased ferritin, Hb, transferrin, and Fe saturation, and TIBC levels in anemic children.Grant Funding Source: Sahmyook University
Comparison of the anti‐inflammatory activities among water extracts of grapefruit, green tea, and cochineal and their microencapsulation particles in RAW 264.7 macrophages
Authors: Jun Yoon-Kyung , Jeon Yeong-Hui , Jiang Yi-Zhang , Kim Myung-Hwan , Nam Seong-Pil , Chang Moon-Jeong 
Published: June 2021

Microencapsulation is a promising processing methods that can increase the surface area, so we expected to increase the physiological effects. Our study aims to evaluate the anti‐inflammatory effects of microcapsules containing water extracts of green tea(WGT), grapefruits(WGF) or cochineal(CCN) in LPS activated RAW 264.7 macrophages. WGT and CCN at the concentration of 0.1–0.3mg/ml, WGF at the concentration of 0.01–0.03mg/ml, that inhibited NO production and decreased the expression of inducible nitric oxide syntase(iNOS) and nuclear factor κB(NF‐κB) without showing cytotoxicity. WGF was considerable more potent than the WGT or CCN. The productions of prostaglandin E_(PGE_) were reduced by the treatments of WGT, WGF or CCN. WGF inhibited LPS‐induced nuclear factor κB to a much greater extent than did WGT or CCN. The processing of the microencapsulation for WGF potentiated the inhibition of anti‐inflammatory effects by water extracts samples, whereas the effects of microencapsulation for WGT or CCN were minimal. The findings presented here suggest that the anti‐inflammatory effect of a grapefruit extract was remarkable and the most potent compared to green tea or cochineal and the microencapsulation enhanced these effects. The results of these investigations indicate possible protective effects against cardiovascular disease and chronic inflammatory diseases.This study was supported by 15 agenda of Korea Rural Development Administration in 2011.
Vitamin K2 administration and bone mineral density in Senescence Accelerated Mice P‐6 (SAMP6)
Authors: Katsuyama Hironobu , Fushimi Shigeko , Yamane Kunikazu , Hinenoya Hajime , Akiyama Yuji , Tomita Masafumi , Okuyama Toshiko , Watanabe Yoko , Katsuyama Midori , Anh Le Ngoc , Saijoh Kiyofumi 
Published: June 2021

The P6 strain of senescence‐accelerated mice (SAMP6) exhibit features of skeletal aging including reduced bone mineral density (BMD), so that various physiological active agents affecting BMD could be examined. In the present study, SAMP6 were used in order to clarify the effect of vitamin K2 on BMD.We developed the further bone resorption model using water‐immersion restraint stress (WRS). Male SAMP6 were divided into three groups, i.e., control group, WRS (6 h/day, 5 times/wk) group, and WRS + vitamin K2 (30 mg/kg s.c.) group. SAMP6 were suffered from this stress between 6 to 10 weeks old. BMD was measured using computed tomography (CT) system for small animals, and bone turnover markers were also examined.BMD of trabecular bone for WRS groups was significantly lower than that of control group, suggesting that WRS was effective to reduce BMD. However, no significant difference of BMD was observed between WRS group and WRS + vitamin K2 group. On the other hand, urinary excretion of CTX, bone resorption marker, was significantly higher in WRS + vitamin K2 group than in other groups. And total osteocalcin in serum was significantly higher in WRS group than in other groups. These results indicated that vitamin K2 could affect bone turnover. This study was supported in part by a Kakenhi (22500684), and a Research Project Grant (No. 22‐A‐59) from Kawasaki Medical School.
Effects of early growth restriction on development and insulin sensitivity in rats
Authors: Ebanks Erica , Lonnerdal Bo , Griffin Ian J. 
Published: June 2021

There is increasing evidence that poor growth of preterm infants is a risk factor for poor long‐term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine consequences of different patterns of postnatal growth and hypothesize that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11 R pups were re‐randomized into litters of 6 (RC; R/catch‐up), 10 (RN; R/normal) or 16 (RR; R/restricted). Pups were weaned at d21. Animals underwent developmental and behavioral tests, including open field maze, T‐Maze and passive avoidance. Insulin sensitivity was measured by i.p. insulin stress test (IPIST) and glucose tolerance test (IPGTT). By d10, N pups weighed 20% more than R pups (p<0.001). By d15, RC caught up to NN pups, RN showed partial catch‐up and RR showed no catch‐up. RR and RC groups showed less explorative behavior during developmental testing3. Further, there was evidence of learning in NN pups during T‐Maze and passive avoidance tests3. Though NN and RR were most insulin sensitive, all R groups were more glucose tolerant compared to NN. In rats, early postnatal growth restriction leads to abnormal development and insulin sensitivity. This “double hit” paradigm may contribute to poor developmental outcomes in preterms.Grant Funding Source: UC Davis Department of Pediatrics
Anthropometric assessment of lactating mothers attending public clinics in the Guatemalan highlands in metropolitan Quetzaltenango
Authors: Oyesiku Linda , Doak Colleen M , Vossenaar Marieke , Solomons Noel W 
Published: June 2021

BackgroundEarly linear growth in Guatemala has historically been compromised, resulting in adults of short stature. A progressive maternal weight change from delivery through lactation has been described.ObjectiveTo assess maternal height and BMI in highland Guatemalan mothers at various periods of lactation.MethodsMaternal weight and height were collected in 543 lactating mothers of infant and toddlers, with subsequent classification of mothers for low‐stature (relative to WHO/NCHS 1985 smoothed curve median) and for underweight (BMI <18.5 kg/m2), overweight (BMI 25–30 kg/m2) or obesity (BMI >30 kg/m2).ResultsMothers ranged in age from 15 to 48 y. The mean stature for the sample was 149.1±5.9 cm, with a median of 149.0 cm and a range, 136.0–169.0 cm. Women classified of Mayan ascent were significantly (p<0.001) shorter (146.9±5.1 cm) than others (150.3±5.9 cm). In terms of height percentiles for the adult reference, 423 (78%) of mothers were below the 5th percentile; 46 (8%) between the 5th and 10th percentile; and only 7 (1%) reached the median. Respective partition for underweight; normal weight; overweight; and obesity was: 4%; 49%; 37% and 10%. Variation in BMI with respect to the age of the offspring was not significant.ConclusionHighland Guatemalan women remain short, with no lactation‐duration effects on BMI.Funded by the Nestlé Foundation and Sight and Life, Switzerland
Maternal and infant iron status in HIV‐infected Malawian women and their exclusively breastfed infants
Authors: Widen Elizabeth M , Bentley ME , Chasela C , Kayira D , Tegha G , Kourtis A , Jamieson D , van der Horst C , Allen L , Shahab-Ferdows S , Adair LS 
Published: June 2021

Identifying infants at risk of early depletion of iron stores is essential to prevent postnatal iron deficiency. Maternal iron status may be a determinant of infant iron status, especially in the context of HIV where iron deficiency is common. We evaluated how iron status of HIV infected Malawian women related to iron status of their exclusively breastfed infants in the Breastfeeding, Antiretroviral and Nutrition Study. Participants were randomized to receive maternal lipid‐based nutrient supplements (LNS), providing 15 mg iron/d, or no LNS, and maternal, infant or no antiretroviral drugs. Infant iron status (Hb, log ferritin, log transferrin receptors TfR) at 2 (n=355) or 6 wk (n=165), and 24 wk (n=532) were regressed on corresponding maternal indicators, each corrected for inflammation (elevated C‐reactive protein and/or α‐1‐acid glycoprotein). Maternal Hb was marginally associated with infant Hb (6 wk β: 0.14, p=0.07; 24 wk β: 0.08, p=0.06). Maternal ferritin was related to infant ferritin only at 2 wk (β: 0.16, p<.01). Maternal TfR was associated with infant TfR at all periods (2 wk β: 0.14, 6 wk β: 0.30, 24 wk β: 0.21; all p<0.001). Maternal LNS predicted marginally lower maternal ferritin at 6 and 24 wk (p<0.1), but not maternal TfR, Hb or infant status. Given the observed maternal influence, optimizing maternal status at delivery and during lactation is important for reducing risk of iron depletion in infants.Grant Funding Source : CDC(U48‐DP000059‐01); Bill & Melinda Gates Foundation(OPP53107); CPC(NICHD 5 R24 HD050924)
The omega and omega‐1 monohydroxyl metabolites of the abused K2/Spice synthetic cannabinoids JWH‐018 and JWH‐ 073 bind with high affinity and act as agonists at human cannabinoid 2 receptors (hCB2s)
Authors: Brents Lisa K , Rajasekaran Maheswari , Franks Lirit , Moran Jeffery H , Prather Paul L 
Published: June 2021

JWH‐018 and JWH‐073 are synthetic cannabinoids present in K2 or Spice, drugs of abuse marketed as incense. These compounds produce psychoactive effects similar to marijuana, but can also result in death and severe adverse effects including hypertension, tachycardia, agitation, anxiety and hallucinations. Recently, we reported that mono‐hydroxylated metabolites of JWH‐018 and JWH‐073 retain high affinity and exhibit a range of activity at cannabinoid 1 receptors (CB1Rs), potentially contributing to the toxicological consequence of K2 use. Since toxicity of these compounds could also result from action at CB2Rs, this study examined the affinity and intrinsic activity of JWH‐018, JWH‐073 and several phase I monohydroxylated metabolites for hCB2Rs stably transfected in CHO cells. Competition binding experiments and functional studies examining CB2R‐mediated G‐protein activation and inhibition of adenylyl cyclase activity indicated that several metabolites retain nanomolar affinity for hCB2Rs and exhibit partial to full CB2R‐agonist activity. Importantly, this included the omega and omega‐1 monohydroxylated metabolites of JWH‐018 and JWH‐073, which are major metabolites excreted in human urine as glucuronide conjugates. Retention of high CB2R affinity and activity post‐metabolism may prolong CB2R activation, resulting in immune system dysregulation.APHL Award (JHM); 1UL1RR029884 (JHM, PLP)
Anti‐hypernociceptive property of the methanolic extract of stems of Kielmeyera rugosa in mice
Authors: Quintans-Junior Lucindo Jose , Melo Monica , Oliveira Makson , Santos Marcio RV , Araujo Adriano AS , Costa Emmanoel V , Anjos Charlene S , Jesus Aline M , Nogueira Paulo CL , Moraes Valeria RS 
Published: June 2021

The present study examined the anti‐hypernociceptive effect of the methanolic extract of stems of Kielmeyera rugosa (MEKR) in mice. For assess this effect were realized models of mechanic hypernociception induced by carrageenan (CG) and substances which mediate the various reactions involved CG, such as TNF‐α, prostaglandin (PGE2) and dopamine (DA). The mice were pretreated with vehicle (saline + Tween 80 0.2%; p.o.) or MEKR (100, 200 and 400 mg/kg, p.o.). Thirty minutes after the treatments, were injected in region subplantar of the rear right paw: 20 μL of CG (300 μg/paw), PGE2 (100 ng/paw), DA (30 μg/paw) or TNF‐α (100 pg/paw). The hypernociception was assessed in times of 0.5, 1, 2 and 3 hours after the injection of CG, TNF‐α, PGE2 and DA, with digital Von Frey. It was observed that MEKR was able to maintain the baseline nociceptive threshold in all tests. The results suggest anti‐hypernociceptive property of MEKR, probably by a mechanism inhibition of production of cytokines, which activate various reactions connected with inflammation, reducing thereby hipernociception.Financial support: FAPITEC/SE, CAPES, CNPq (Brazil).
Effects of Fresh and Aged Traffic‐Related Particles on Breathing Pattern, Cellular Responses and Oxidative Stress
Authors: Diaz Edgar A. , Chung Yeonseung , Lamoureux Denise P , Papapostolou Vasileios , Lawrence Joy , Long Mark s , Sato Rodrigo , Joao Oliveira , Godleski John J 
Published: June 2021

BackgroundAir pollution is a mixture of gaseous and particulate pollutants emitted from multiple sources. During transport in the atmosphere, emissions undergo photochemical reactions that may render them more harmful.ObjectivesThe aim of this study was to investigate the toxicity of primary and secondary traffic particles.MethodsSprague‐Dawley rats were exposed to either: fresh primary particles from a tunnel plenum (P); secondary organic aerosol formed from photochemical oxidation of primary gases after filtration of primary particles (SOA); photochemically aged primary particles plus secondary organic aerosol (P + SOA); or filtered clean air. In each exposure, pollutant gases were removed using a non‐selective denuder.Animals were exposed for 5 hours/day, with varying numbers of days of exposure. Outcomes included breathing pattern, in‐vivo chemiluminescence (IVCL), broncho‐alveolar lavage, and complete blood count.ResultsMass concentration was ~50μg/m3. Respiratory data showed many changes with each exposure type. All produced decreases in tidal/minute volumes and inspiratory/expiratory flows. There were mild inflammatory changes in BAL, with increased neutrophils for SOA and P+SOA and lymphocytes for P and P+SOA, without changes in total protein, β‐NAG or IVCL.ConclusionsAll exposures produced changes compared to filtered air; overall toxicity, P+SOA>P>SOA.
Critical Role of Transglutaminase 2 in Endothelial Cell Inflammation and Lung PMN Sequestration
Authors: Bijli Kaiser M , Kanter Bryce G , Xu Lei , Fazal Fabeha , Rahman Arshad 
Published: June 2021

We addressed the role of transglutaminase2 (TG2), an enzyme that catalyzes protein crosslinking reactions, in causing endothelial cell (EC) inflammation. Exposure of EC to thrombin resulted in activation of the transcription factor NF‐κB and its target genes, vascular cell adhesion molecule‐1 (VCAM‐1) and interleukin‐6 (IL‐6). RNAi knockdown of TG2 inhibited thrombin‐induced NF‐κB activity and expression of VCAM‐1 and IL‐6. Analysis of NF‐κB pathway revealed that TG2 depletion had no effect on IκBα phosphorylation/degradation and NF‐κB DNA binding function. Interestingly, TG2 knockdown impaired thrombin‐induced phosphorylation of RelA/p65 at Ser536, a crucial event that confers transcriptional competency to the DNA‐bound NF‐κB. Thus, TG2 mediates EC inflammation by promoting the transcriptional activity of NF‐κB. Because thrombin is released in high amounts during sepsis and its concentration is elevated in plasma and lavage fluids of patients with Acute Respiratory Distress Syndrome (ARDS), we determined the in vivo relevance of TG2 in a mouse model of sepsis‐induced lung PMN recruitment. A marked reduction in ICAM‐1 expression and lung PMN sequestration was observed in TG2 knockout compared to wild type mice after intraperitoneal lipopolyschharides (LPS) challenge. Together, these results identify TG2 as an important mediator of lung vascular inflammation associated with sepsis.Sponsors: NIH (HL067424 and HL096907) and AHA SDG grant.