bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms underlying antinociception exerted by endomorphin in the spinal dorsal horn
Authors: Li Yun-Qing 
Published: June 2021

BackgroundEndomorphin (EM) is a new opioid peptide and considered as the endogenous ligand for the mu‐opioid receptor (MOR) with high affinity. EM has similar effect in pain inhibition as morphine, but with much less side effects. In the dorsal root ganglion (DRG) and superficial layers (laminae I and II) of the spinal dorsal horn, many substance P (SP), EM and MOR immunpositive neurons and dense fibers and terminals are found, respectively. Based on these phenomena, we proposed a hypothesis that EM binding to its autoreceptor MOR on the pre‐synaptic buttons will inhibit further release of the noxious neurotransmitters, such as SP.AimsTo prove whether the hypothesis is true or not, the antinociceptive effects of EM through pre‐synaptic mechanism in the superficial layers of the spinal dorsal horn were investigated.MethodsBehavioral observation, whole‐cell patch clamp recording, immunofluorescent histochemistry and post‐embedding immunohistochemical staining methods were used.Results(1) EM pre‐treatment through intrathecal administration could dose‐dependent inhibit the primary mechanical allodynia induced by subcutaneous injection of complete Freund's adjuvant (CFA). This effect might be reversed by antagonists of neurokinin 1 receptor, and attenuated by SP or co‐administration of SP and EM, respectively. (2) EM remarkably reduced the frequency instead of the amplitude of miniature EPSCs in lamina II. This effect was antagonized by MOR antagonist beta‐FNA. EM could also inhibit the EPSCs induced by stimulating of the attached dorsal root. The average amplitude of the residual EPSCs increased during high concentration of SP being perfused. (3) SP, EM and MOR were co‐localized in the DRG neurons. SP and EM were observed within the same large dense‐coated granular synaptic vesicles in the pre‐synaptic buttons, whereas MOR was localized on the pre‐synaptic membrane of the pre‐synaptic buttons in which SP and EM were found to co‐exist in the same vesicles.ConclusionsSP and EM are co‐localized in the pre‐synaptic button, of which MOR can be found on the pre‐synaptic membrane. EM inhibits excitatory synaptic transmission and decreases the release of SP from primary afferent terminals in the superficial layers of the spinal dorsal horn through activating MOR on primary afferent terminals to exert their analgesic effects.
Flavan‐3‐ol isolated from rhizome of Drynaria fortunei (Kunze) J. Sm. exerts osteoprotective effects via its actions on osteoblastogenesis and osteoclastogenesis
Authors: Wong Man-Sau , Wong Ka-Chun , Dong Xiaoli , Law Man-Chun , Chan Tak-Hang 
Published: June 2021

(‐)‐Epiafzelechin (FRD) is a flavan‐3‐ol found in rhizome of Drynaria fortunei (Kunze) J. Sm., a Chinese herb commonly used for management of bone diseases. Previous study suggested FRD could stimulate osteoblastic functions. Our study aims to determine if FRD act on osteoblastogenesis and osteoclastogenesis, and if its actions in bone cells involve the activation of Estrogen Receptors (ER) using pre‐osteoblast MC3T3‐E1, pre‐osteoclast RAW 264.7 as well as osteoblast‐like UMR 106 cells. FRD could increase alkaline phosphatase activity and secretory collagen in MC3T3‐E1 cells.FRD could reduce viability of RAW 264.7 cells and prevent the formation of osteoclastic cells, as observed by a reduction of Tartrate‐resistant acid phosphatase activity. Co‐incubation of ER antagonist (ICI 182780) with FRD abolished its positive effects on UMR 106 cell growth. FRD has a weak binding affinity to ER‐alpha and beta and could only weakly activate ER‐alpha, but not ER‐beta, mediated Estrogen Response Element (ERE)‐dependent transcriptional activity in UMR 106 cells.In conclusion, our results showed that FRD could stimulate osteoblastogenesis and inhibit osteoclastogenesis and its positive effects in bone cells appeared to be ER dependent.Funding support: RGC General Research Fund [POLYU 563209] and research studentship from the Hong Kong Polytechnic University
Effects of high‐fat diet on intestinal permeability and inflammation‐associated tumorigenesis
Authors: Kim Min-Young , Bae Yun-Jung , Bak Youn-Kyung , Kim Jin , Sung Mi-Kyung 
Published: June 2021

High‐fat diet induces “chronic low‐grade” inflammation and oxidative stress. Intestinal barrier plays an important role and its disruption leads to the increased permeability implicated pathogenic changes in several diseases. The aim of this study was to investigate the effects of high‐fat diet on intestinal permeability and carcinogenesis. APCmin+/− mice were fed with normal diet(ND) or high fat diet(HD), to examine intestinal permeability and tumorigenesis. Although there was no significant difference in body weight, the total tumor number was higher in HD group than that of ND group. Plasma total antioxidant capacity was lower in HD group, while 8‐OHdG level was higher. Protein expressions of ZO‐1, claudin‐1 and occludin were lower in HD group suggesting intestinal permeability was increased. Plasma MPO and IL‐6 levels were higher in HD group than those of ND group. CD14, the only LPS receptor, plasma level and colonic TLR4 mRNA expression were increased in HD group than ND group. These results suggest that high‐fat diet increases oxidative stress and inflammation induced by endotoxemia disrupting intestinal gap junction proteins which increase membrane permeability and accelerating tumorigenesis. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology (2010‐0000918) and the SRC program(Center for Food&Nutritional Genomics:2011‐0000918) of the National Research Foundation(NRF) of Korea funded by MEST.]Grant Funding Source : Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education,Science and Technology (2010‐ 0000918) and the SRC program(Center for Food&Nutritional Genomics:2011‐0000918) of the National Research Foundation(NRF) of Korea funded by MEST
Association of the Parental Feeding Practices and Type and Home Availability of Sugar‐Sweetened Beverages and Fruit Juice of Preschool Children from Low Income Families
Authors: Lora Karina , Quesada Catalina , Wakefield Dorothy , Ferris Ann 
Published: June 2021

This study evaluated the association of parental feeding practices with home availability and children's reported portion size (PS) of sugar‐sweetened beverages (SSBs): juice drinks, soda, and fruit juice (FJ) for 300 poor parents of 3–5 y. old children. Participants provided demographic and anthropometric data, completed the Preschooler Feeding Questionnaire (PFQ) (Baughcum et al, 2001) and an inventory of beverages in the home. PFQ Factor analysis retained eight factors for 31 questions. Multivariate regression models tested if PFQ factors predicted child's daily PS of SSBs and FJ while controlling for demographic variables. Child's reported daily PS (oz) were 16.2±15.4 fruit juice, 13.8± 12.0 juice drinks, and 1.43±3.2 soda and were correlated with home availability. Higher structure during feeding interactions was associated with lower reported consumption of SSBs by the child. Latino parents were significantly more child‐centric, used more rewards, and more likely to feed older children inappropriate foods than African‐American parents. Being a young parent (19–25 y) and SNAP participant was positively associated with home availability of juice drinks and child's reported PS. Parents’ education was negatively associated with child's soda PS (P< .05). Fewer SSBs were available in the homes of parents with controlled feeding practices.Grant Funding Source : USDA/NRI 2008‐55215‐19071
Characterization of flavanol and procyanidin absorption and metabolism in humans: identification of potential bioactive metabolites
Authors: Ottaviani Javier Ignacio , Momma Tony Y. , Keen Carl L. , Schroeter Hagen 
Published: June 2021

Accumulating data suggest a causal relationship between diets rich in flavanols (F) and procyanidins (P) and cardiovascular health in humans. Thus, it becomes important to understand the absorption, distribution, metabolism and excretion (ADME) of these food constituents. F and P encompass a complex group of phytonutrients, including 4 F stereoisomers, and various P, consisting of F oligomers of different chain lengths. In this study, we assessed metabolism and the systemic concentrations of F stereoisomers and P in humans, following the intake of these compounds in a well‐characterized food matrix. The results show that the ADME of F is stereoisomer‐specific. Moreover, F stereochemistry and metabolism represented major determinants for the vasodilation activity of these compounds in vivo. Compared to F, P reached negligible levels in circulation. Contrary to previous suppositions, P did not contribute to the systemic presence of F via depolymerization in the gastrointestinal tract. However, 5‐(3,4‐dihydroxyphenyl)‐γ‐valerolactone, a gut microbiome‐related catabolite, was detected after the intake of F and P. Taken together, our results argue for a more comprehensive discrimination between the F and P content in foods, which may result in the identification of clearer epidemiological outcomes, and a better understanding of the putative nutritional and health‐promoting properties of F and P in general.Grant Funding Source: Mars, Inc
The immunological cellular and biochemical contents of breastmilk respond to maternal or infant infections
Authors: Hassiotou Foteini , Metzger Philipp , Trengove Naomi , Lai Ching Tat , Hartmann Peter , Filgueira Luis 
Published: June 2021

Breastmilk contains immunological components that protect the infant. Among those, leukocytes have been variably present in breastmilk. To examine whether this variability may be related to the health status of the mother/infant dyad, mature breastmilk was collected from 20 dyads longitudinally, while they were healthy and while they had an infection. Leukocyte content was measured by flow cytometry via the pan‐leukocyte marker CD45. Breastmilk from healthy dyads had 0–1.5% of leukocytes (0–1,365 immune cells/mL breastmilk). During an infection of the mother and/or the infant, leukocyte content increased to up to 94% of total cells (2,594,982 leukocytes/mL breastmilk), with the majority of leukocytes being activated T‐cells that responded to viral peptides if stimulated in vitro, with corresponding proliferation and cytokine secretion. Interestingly, leukocyte content returned to baseline levels (≤1.5%) upon recovery from the infection. Similar responses were observed for immunoglobulins and lactoferrin. Despite their higher concentrations in mothers weaning or very late into lactation, leukocyte content remained low (0–1.5%) under healthy conditions. It is concluded that infection induces a rapid mechanism of leukocyte movement into breastmilk, followed by a biochemical response. Unless induced by infection, leukocytes are either absent or present in very small amounts in mature breastmilk.Grant Funding Source : Women and Infants Research Foundation, Medela AG
Innate immune signaling plays a crucial role in the pathogenesis of avascular osteonecrosis of the femoral head
Authors: Okazaki Shunichiro , Nagoya Satoshi , Tateda Kenji , Katada Ryuichi , Mizuo Keisuke , Watanabe Satoshi , Yamashita Toshihiko 
Published: June 2021

ObjectivesPathogenesis of avascular osteonecrosis of the femoral head (ONF) still remains unclear. We hypothesized that innate immune signaling via toll‐like receptor (TLR) play any role in pathogenesis of ONF. We found that administration of ligands of TLR with steroid treatment induces ONF. The present study verified the hypothesis and evaluated effect of steroid in the development of the ONF.MethodsMale Wistar rats (n=120) were randomly divided six groups. Each group rats were given saline or ligands of TLR on day 1 and saline or methylprednisolone on day 2. Animals were sacrificed 1, 3, 7 or 14 days after last injection. Histopathological, biochemical analyses were then performed.ResultsONF was observed in groups given ligands of TLR and methylprednisolone treatment. Although the activity of IRF7 did not change, the activity of NF‐κB was decreased after methylprednisolone injection.ConclusionsThe present study shows that the innate immunity signaling pathway via the TLR, especially MyD88 dependent pathway may play a crucial role in pathogenesis of ONF.
Development of a new chick chorioallantoic membrane model for human pancreas adenocarcinoma
Authors: CASTRONOVO Vincent , GONZALEZ Arnaud , DELVENNE Philippe , PEULEN Olivier 
Published: June 2021

Pancreatic cancer is the fourth leading cause of cancer death in developed countries. Early‐stage pancreatic cancer is usually clinically silent, and disease only becomes apparent after the tumor invades surrounding tissues or metastasizes to distant organs. One of the urgent challenges in pancreas cancer research is to set up model systems allowing the development and testing of new therapies as well as the discovery of new diagnostic markers. The chick chorioallantoic membrane (CAM) has been successfully used to produce tumors from various cancer cell lines. Here, using BxPC3 human pancreatic cells we were able to produce within 7 days post‐grafting 30 mm3vascularized tumor on CAM. Histology analysis revealed that the cancer cells formed tumors compatible with PanIN‐3 grade human malignant adenocarcinomas. Immunohistochemistry revealed that the malignant cells were positive for carcinoembryonic antigen and cytokeratin‐7, and ‐19. Functional blood vessels were numerous between pancreatic islets. Interestingly, we were able to demonstrate that two biomarkers recently identified in our lab from human pancreas cancer tissues, latent‐transforming growth factor beta‐binding protein 2 (LTBP‐2) and transforming growth factor beta‐induced (TGFBI) were found to be also expressed in the BxPC3. The possibility to perfuse the tumor allows to expect this model to be used to detect new biomarkers as well as inject and test drugs.This work was support by the Fond Léon‐Fredericq (ULg) and FNRS.
Acceptance and usefulness of an audience response system in teaching an undergraduate pharmacology class
Authors: Sekar M. Chandra 
Published: June 2021

At all levels of education, teachers are encouraged to promote the concept of active learning in their classrooms and curriculums. Use of an audience response system encourages greater participation of the audience and should therefore stimulate learning.Senior students, enrolled in the fourth year of their six‐year Pharm D program at the University of Findlay, were required to bring “clickers” for each of my classes in the cardiovascular disease module. While students were not graded for their answers, positive incentives in the form of participation points were awarded.Forty‐eight of the fifty‐four students completed the anonymous Google Docs survey, the results of which are presented below:

Question
Response %

SA
A
D
SD
NA

Promoted learning
73
23
0
0
0

Improved concentration
40
54
6
0
0

Class more interesting
46
48
2
0
0

Identified difficult to understand concepts
52
44
4
0
0

Wrong answer explanation helped me to learn
38
56
2
4
0

Results clearly indicate that over 90% of the students believed clicker use in the class made the class more interesting and promoted learning.
Immune synapse malformation: Role for CAV1 and PAK1
Authors: Gilling Christine Elizabeth , Mittal Amit K , Joshi Shantaram S 
Published: June 2021

Caveolin‐1 (CAV1) a scaffold molecule, is a member of the tolerogenic signature and is significantly differentially expressed in chronic lymphocytic leukemia (CLL). CAV1 controls transmembrane signaling and has been hypothesized to regulate actin polymerization. Additionally, impaired immune synapse (IS) formation has been reported in CLL. Therefore the objective of this report was to identify the molecular basis of IS malformation in CLL. We hypothesized that IS malformation is caused by dysregulation of cytoskeletal molecules associated with CAV1. Ingenuity pathway analyses of differentially expressed cytoskeletal molecules in CLL cells revealed direct association of ARPC5, CALD1, CASK, DSTN, PFN2, STMN1, VASP, and WAS with CAV1. Further, high expression of CAV1 and DSTN were clinically correlated with a poor prognosis (p=0.047 and p=0.007, respectively). CAV1 knockdown in Raji and Jurkat cells, a model for IS formation, resulted in decreased IS formation with decreased expression of F‐actin (involved in actin polymerization) and PAK1 (associated with cell protrusions). Together, our results suggest a role for CAV1 in regulating immune synapse formation by regulating F‐actin and PAK1 molecules.Grant Funding Source : Supported by the CLL Foundation, Houston, TX and the NIH INBRE grant P20 RR016469.
Tubulobulbar Complexes Formed In Sertoli Cells In Primary Cultures Associate With Intercellular Junction Elements
Authors: Du Min , Roskelley Calvin , Nicholls Peter , Stanton Peter , Deng Wanyin , Finlay Brett , Vogl Wayne 
Published: June 2021

In the seminiferous epithelium, unique double membrane structures termed tubulobulbar complexes (TBCs) develop in association with basal junction complexes. These actin‐related structures are proposed to internalize intercellular junctions during the movement of spermatocytes from basal to adluminal compartments of the epithelium. To study the role of basal TBCs in junction turnover, we use a primary Sertoli cell culture system in which TBCs develop in the vicinity of junction complexes between Sertoli cells. We immunoprobed cultured Sertoli cells for the intercellular junction elements Claudin‐11, Connexin‐43 and Nectin‐2 and discovered rod‐like structures that protrude into Sertoli cells from the cell periphery. These protrusions resemble TBCs that form in the intact seminiferous epithelium. These protrusions also co‐localize with F‐actin, which is known to associate with the proximal tubular part of TBCs and can be used as a marker for TBCs. Significantly, cultured Sertoli cells that express GFP‐tagged Claudin‐11 and Connexin‐43 extend similar protrusions into neighboring non‐transfected Sertoli cells. Our results are consistent both with the conclusion that junction elements from neighboring Sertoli cells are found together within TBCs, and with the hypothesis that tubulobulbar complexes may play a role in the turnover of intercellular junctions. Supported by an NSERC Discovery Grant to AWV.Grant Funding Source : NSERC
Bacterial LPS Influences Receptor Activator NF Kappa B and Fractalkine Receptors Expression In Arterial Smooth Muscle Cells Derived From Limbs Amputated For Peripheral Arterial Disease
Authors: Zamin Rasheeda , Norman Paul , Filgueira Luis 
Published: June 2021

Bacterial infections may trigger peripheral arterial disease (PAD) through their lipopolysaccharide (LPS) molecules by changing expression of CX3CR1 and RANK, which are associated with atherosclerosis and arterial calcification.Arterial samples were harvested from 9 patients undergoing lower limb amputation for PAD. We initially identified the presence of bacterial (chlamydia and mycoplasm) antigens/LPS and inflammatory markers (CX3CR1 and RANK) in tissue samples using immunofluorescence staining. Secondly, the effect of LPS was tested in vitro (10ng/ml) using proliferating primary human arterial smooth muscle cells (pASMC). The expression of CX3CR1 and RANK post‐activation, with or without LPS, was assessed on 2 different pASMC cell lines using flow cytometry.All samples showed evidence of infection. RANK and CX3CR1 were expressed in all arterial samples. Flow data showed that LPS down‐regulated RANK expression on pASMC (0.52–0.62 reduction in standardized mean intensity), while CX3CR1 expression was up regulated (1.27–1.75 increment) compared to non‐activated pASMC.Our studies suggest that LPS may induce inflammatory changes seen in PAD lesions. Down‐regulation of RANK may play a role in calcification of infected arteries, while up regulation of CX3CR1 may contribute to the atherosclerotic changes.
Creation, Implementation, and Evaluation of a Neuroscience Curriculum for Grades 4–6
Authors: Rider Kristina , Dao Kim , Puder Barb 
Published: June 2021

Anatomical sciences education requirements for grades K‐12 have recently been updated at state and national levels. At the local school level, many school systems are unable to fulfill the anatomical sciences education requirements due to financial constraints and/or lack of anatomical knowledge by the classroom teacher. Current research indicates that a neuroscience curriculum has not been developed and implemented in the academic instruction of students in grades K‐12. This prospective study involved developing a four‐week neuroscience curriculum targeted to students in grades 4–6 and determining if the curriculum was effective in outlining neuroscience concepts. The curriculum was presented to the 5th grade classrooms of a pre‐selected Oakland, CA area elementary school. During each one hour weekly session, the students were presented a neuroscience topic which was reinforced with interactive hands‐on activities and take home assignments. To assess the effectiveness of the curriculum, anonymous pre and post tests were administered and statistical significance was achieved using paired sample T –tests. Upon analysis of the data, the neuroscience curriculum allows students to retain neuroscience concepts and supports part of the anatomical sciences requirements currently mandated by state and national agencies.Grant Funding Source : none
Double‐stranded breaks in S. cerevisiae: recruitment of TFIIH and stability of DNA ends
Authors: Wolstencroft Paige Wheaton , Negritto M. Cristina 
Published: June 2021

Transcription factor IIH (TFIIH), with known functions in the nucleotide excision repair pathway (NER) and transcription initiation, has been implicated as having a role in the repair of Double Strand Breaks (DSBs) in S. cerevisiae. The Bailis research group identified the Rad3 helicase, a subunit of TFIIH, as an important factor in suppressing short sequence recombination (SSR). The RAD3 mutant, rad3‐G595R, has been shown to increase the frequency of SSR by increasing the stability of DSB ends. In this study we set to determine if TFIIH is physically present at DSBs such that it could be directly affecting DNA end processing. Chromatin immunoprecipitation (ChIP) assays were used to study the recruitment of TFIIH to the site of DSBs in both wildtype and rad3‐G595R mutant strains. Our results indicate that in wild type strains the level of TFIIH at the site of the break increases after a DSB has been induced and then gradually declines once the break stops being induced. However, in a rad3‐G595R mutant there is no significant increase in TFIIH localization following DSB induction. By verifying the presence of TFIIH at DSBs, a role for this complex in dealing with the repair of DSBs has been confirmed. The faulty recruitment observed in the mutant strain helps postulate new ideas on the exact role TFIIH may be playing in DSB repair.(Funding: Pomona College Summer Undergraduate Research Program)