bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant Capacity and Stability of Phenolic Compounds in Aronia Kefir during in vitro Digestion
Authors: Du Xue , Myracle Angela D
Published: November 2023

Aronia (Aronia melanocarpa) is an underutilized berry that is rich in bioactive compounds, such as anthocyanins and phenolic acids. Phenolic compounds are strong antioxidants that may provide health benefits for chronic diseases, such as type 2 diabetes. Kefir is a fermented dairy beverage which contains several species of live micro‐organisms and may help to maintain gut health. The live microbes in kefir create a dynamic environment with an acidic pH which could protect the anthocyanins in aronia from degradation. In this study, aronia juice was incorporated into a fermented kefir product. Aronia kefir was subjected to an in vitro digestion process to evaluate the antioxidant capacity, stability of bioactive components and the potential effects on carbohydrate‐hydrolyzing enzymes. Mouth, stomach, and small intestinal environments were simulated using corresponding digestive juices (containing enzymes) where pH, time and temperature were controlled. An aliquot was removed from each step for analysis. UPLC‐DAD was used to quantify anthocyanins and phenolic acids in each fraction. The antioxidant capacity was measured using 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging assay. The inhibitory effects of digested aronia kefir on carbohydrate‐hydrolyzing enzymes were assessed by measuring the IC20 values against α‐amylase and IC50 values against α‐glucosidase. The control sample was processed under the same conditions with the absence of digestive enzymes. The results of this study showed that mouth digestion did not alter the quantity of phenolic compounds or the antioxidant capacity of aronia kefir. After gastric digestion, the amount of phenolic compounds was elevated compared to the mouth digesta, which led to an improvement in the antioxidant capacity. Intestinal digestion resulted in a slight increase in cyanidin‐3‐galactoside and a decrease in neo‐chlorogenic acid. The amount of chlorogenic acid was enhanced significantly compared to gastric digesta. Antioxidant capacity of intestinal digesta was also improved. After digestion, aronia kefir exhibited strong inhibitory activity toward α‐glucosidase and moderate inhibition to α‐amylase. This result indicates that digested aronia kefir has the potential to decrease or slow the absorption of carbohydrates, thus helping to maintain blood glucose levels. This study demonstrates that accessible anthocyanins and phenolic acids in aronia kefir were stable during digestion and exhibited high antioxidant capacity. Hence, incorporating aronia kefir into a healthy diet is potentially beneficial to diabetic patients to help decrease oxidative stress and to better control their blood glucose level.

Support or Funding Information

University of Maine start up funds
In vitro antidiabetic activities of dioecious White mulberry (Morus alba, Moraceae)
Authors: Basu Paramita , Thallapareddy Charitha , Maier Camelia
Published: November 2023

Diabetes mellitus is an endocrine and metabolic disorder resulting from defects in both regulations of insulin secretion and/or insulin action and is characterized by chronic hyperglycemia, dyslipidemia, and protein metabolism. Consumption of high‐carbohydrate diets is one of the causes for elevated postprandial hyperglycemia leading to the development of type 2 diabetes. The inhibition of intestinal α‐glucosidase, which digests disaccharides and starch, and α‐amylase, which breaks down starch and glycogen, has been associated with preventing carbohydrate digestion to absorbable glucose. Leaves of White mulberry (Morus alba, Moraceae) have been used in traditional medicine to treat diabetes. In the present study, ethanol extracts from both leaves and stems collected in spring and fall were evaluated for their α‐amylase and α‐glucosidase inhibitory activities. All extracts (10 mg/ml), with the exception of the fall female stem extract, inhibited both α‐amylase and α‐glucosidase activities by at least 50%. The highest in vitro α‐amylase inhibitory activities were displayed by spring male and female leaf extracts (10 mg/ml) which inhibited the enzyme activity by 69% and 67%, respectively. The in vitro α‐amylase inhibitory activities of the other extracts (10 mg/ml) ranked as follows: fall female stem (65%) and spring female stem (62%) > fall male leaf (60%) > spring male stem (54%) > fall male stem (50%) and fall female leaf (49%). The highest α‐glucosidase inhibitory activities were displayed by fall female leaf, fall male leaf, and spring male leaf extracts which inhibited the enzyme activity by 86%, 84%, and 82%, respectively. The α‐glucosidase inhibitory activities of other extracts ranked as follows: fall male stem (72%) > spring female leaf (59%), spring male stem (55%), and spring female stem (50%) > fall female stem (41%). The most potent α‐amylase inhibitory IC50 value was displayed by fall female stem (IC50 2.56 mg/ml) and spring male and female leaf (IC50 2.43 mg/ml) extracts. The α‐amylase inhibitory IC50 values for the other extracts ranged from 3.03– 10.85 mg/ml. The most potent α‐glucosidase inhibitory IC50 value was displayed by spring male leaf extract (IC50 2.13 mg/ml). The α‐glucosidase inhibitory IC50 values for other extracts ranged from 5.3–7.57 mg/ml. In general, spring extracts showed significantly higher α‐amylase inhibitory activity as compared to the fall extracts, whereas for α‐glucosidase, fall extracts showed significantly higher inhibitory activity as compared to spring extracts. Both spring and fall male and female leaf extracts are more potent at inhibiting the activities of α‐amylase and α‐glucosidase than the corresponding stem extracts. The results of this study showed that growing season and gender of mulberry specimens could influence their antidiabetic properties and could be used in formulating more potent antidiabetic dietary supplements.
Activation of Nrf2 Target Genes by Aged Garlic Extract in THP‐1 Macrophages: Regulation by Glutathione Depletion
Authors: Eudy Brandon J , Carter Robert E , Abed Sawsan A , Svoboda Steven A , Percival Susan S
Published: November 2023

Garlic products, including aged garlic extract (AGE) have been shown to have antioxidant and anti‐inflammatory activities, which arise from activation of the Nrf2‐antioxidant response element (ARE) pathway. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is typically activated during oxidative stress, but may also be activated by dietary electrophilic molecules, such as those found in AGE, suggesting multiple mechanisms of Nrf2 activation. It is not known whether glutathione (GSH) antioxidant capacity affects the cellular Nrf2 response to AGE. To test this, we investigated whether augmentation or depletion of intracellular GSH would affect the Nrf2‐ARE pathway in THP‐1 macrophages after treatment with AGE. We prepared AGE by dissolving commercially available tablets in deionized water at pH 2.0 overnight. The slurry was centrifuged and the clarified supernatant was used for treatments. Prior to treatment with AGE, intracellular GSH was increased by incubating the THP‐1 cells with exogenous GSH, or decreased by incubation with buthionine sulfoximine (BSO). Macrophages treated with AGE showed increased nuclear accumulation of Nrf2 by western blotting. Nrf2 target gene expression was measured using RT‐qPCR. All THP‐1 macrophages treated with AGE showed increased expression of NADPH quinone oxidoreductase 1 (NQO1). Heme oxygenase 1 (HO‐1) was only upregulated in macrophages pre‐treated with BSO. These data show that macrophages with augmented GSH concentrations still responded to treatment with AGE by upregulating Nrf2 target genes, while GSH depletion further increased expression of HO‐1. These data agree with other studies showing that oxidative stress may not be required for Nrf2 activation and that dietary electrophiles, such as those found in AGE, may be able to activate Nrf2 in the absence of oxidative stress.

Support or Funding Information

UF‐IFAS Agricultural Experiment Station
Cirsium setidens Nakai extract suppresses adipogenesis and regulates lipid metabolism genes in 3T3‐L1 cells
Authors: Cho Bong‐Yeon , Lee Jin‐Ha , Kim Jae‐Min , Choi Sun‐Il , Jung Tae‐Dong , Choi Seung‐Hyun , Ra Moon‐Jin , Kim Sun‐Young , Kang Il‐Jun , Han Kyoung Chan , Lee Ok‐Hwan
Published: November 2023

Cirsium setidens Nakai, a wild perennial herb, grows mainly in Kangwon province, Korea, and it has been reported to contain bioactive ingredients with various medicinal activities including treat edema, bleeding and hemoptysis. However, the potentiality of anti‐obesity effects of C. setidens Nakai has not been fully investigated. To characterize anti‐obesity effect of C. setidens Nakai extract (CNE) and to evaluate its potential as a functional food, we performed various obesity‐related in vitro experiments. In adipogenesis assay, CNE blocked the differentiation of 3T3‐L1 preadipocyte in a dose‐dependent manner. Exposure 200 μg/mL, CNE significantly reduced lipid accumulation (~40%). In addition, CNE suppressed the expression of lipogenic genes, while increasing the expression of lipolytic genes. The anti‐adipogenic and anti‐lipogenic effect of CNE seems to be mediated by the inhibition of PPARγ and C/EBPα, C/EBPβ, C/EBPδ expression. Moreover, CNE stimulated fatty acid oxidation in an AMPK‐dependent manner. These results showed anti‐obesity effects of CNE on adipogenesis and lipid metabolism in vitro and raised a possibility of developing the treatment of obesity as non‐toxic natural resources.
Communication Skills Development through Experiential Learning in Nutritional Sciences
Authors: Nojima Akiko , Ravia Jennifer , Hongu Nobuko
Published: November 2023

Purpose

Effective communication skills are recognized as crucial for the successful future career of college graduates. The purpose of this study was to examine the communication skills in undergraduate nutrition students and explore the ideas how Experiential Learning class (i.e. offers undergraduate students work opportunities outside of classroom in addition to the classroom lectures in Nutritional Sciences), could help improving student's communication skills throughout the semester.

Methods

The 5‐minute surveys were distributed to the students who were taking Experimental Learning class. Most of these students were Junior or Senior in nutrition majors who plan to pursue a career in the field of dietetics. The survey was composed of 21 statements asking about their feeling of public speaking (e.g. enjoy, good at, terrified, tense, etc.) at 3 types of communication events (one‐on‐one, small group, large group – public speaking). In addition, these students were asked to have a 10‐minute face‐to‐face interview conducted by the interviewer (PI) at the end of semester. At the face‐to‐face interview, the students were asked what activities were most effective to improve their communication skills through Experiential Learning class, and what made students gain confidence at public speaking. Data were analyze with descriptive and multiple liner regression.

Results

45 students answered the survey both at the beginning and the end of the semester and 24 students volunteered to have the face‐to‐face interview. At the beginning of the semester, 22% of students (n=10) reported high degree of anxiety (e.g., terrified of speaking in public), and 42% of students (n=19) reported moderate degree of anxiety (e.g., I avoid speaking in public, if possible) in public speaking. At the end of semester, numbers of students who had moderate degree of anxiety in public speaking decreased significantly (29%, n=13, p<0.05), but the numbers of students who had high degree of anxiety did not change. Also, at the end of semester none of students reported high degree of anxiety in a small group speaking. In the face‐to‐face interviews the students who had high and medium degree of anxiety reported the Experiential Learning course provided opportunities and helped to improve their talking and meeting new people, but they wanted more feedbacks or instructions how to improve their communication skills.

Conclusions

The Experiential Learning course in Nutritional Sciences is an effective way to improve communication skills in dietetic students. The results of this study will further contribute to develop teaching materials for students who have high and medium degrees of anxiety in public speaking.

Support or Funding Information

International Research Fund ‐ Ritsumeikan University
PSEN1 as an Adjunct for Diagnosis of Human Myocarditis
Authors: Hanson Paul J , Jang Erika L , Rai Harpreet , Chang Angela Y , Mo Angela Y , McManus Bruce M , Seidman Michael A
Published: November 2023

Background

Myocarditis, defined as inflammation of the heart muscle, is a spectrum of conditions causing considerable morbidity and mortality, resulting from various etiologies, including infection, autoimmunity, or chemical exposure. As such, diagnosing myocarditis can be quite difficult and determining etiology even more so. The gold standard of diagnosis is endomyocardial biopsy showing inflammation with or without myocyte damage in the absence of an ischemic event. However, due to the spatial and structural heterogeneity of myocarditis, diagnostic sensitivity is estimated as low as 30%. To improve upon this, we examined several markers implicated in the pathogenesis of viral myocarditis in animal models as possible diagnostic adjuncts. PSEN1 (the gene encoding presenilin 1) emerged as a promising candidate. This study aims to formally evaluate PSEN1 as a diagnostic adjunct.

Design

Fifty (50) cases were examined for PSEN1 staining (20 lymphocytic active or healing myocarditis, 4 eosinophilic myocarditis, 4 idiopathic dilated cardiomyopathy, 4 hypertrophic cardiomyopathy, 4 sarcoidosis, 4 coronary artery disease, 3 transplant rejection, 1 Lyme disease, 1 toxoplasmosis, and 5 normal controls). All cases were obtained from the Cardiovascular Tissue Registry in the Centre for Heart Lung Innovation, under approved human ethics protocols. Levels of PSEN1 were evaluated using colour segmentation and scoring conducted by three individual subspecialty cardiac pathologists blinded to diagnosis. Statistical analysis was performed using Mann Whitney U test and receiver operating characteristics (ROC) curves.

Results

Colour segmentation and pathologist scoring correlated with each other well (Spearman's rho correlation coefficient 0.71 or better in all comparisons). PSEN1 is expressed at significantly higher levels in lymphocytic myocarditis cases as compared to normals and to all other pathologies (all pvalues less than 0.005). The ROC curves for diagnosing myocarditis as compared to other pathologies using PSEN1 staining have areas under the curve (AUCs, or cstatistics) ranging from 0.78 to 0.88. Of note, several “false positive” cases were those with idiopathic dilated cardiomyopathy, such cardiomyopathy reflects the end stage of a prior lymphocytic myocarditis. Case subset analyses and validation on biopsy specimens are under way.

Conclusion

PSEN1 immunohistochemistry appears to be a helpful diagnostic adjunct for identifying myocarditis, even in minimally inflamed specimens and in tissue obtained long after the initial insult.

Support or Funding Information

Funding and support from St. Paul's Foundation
Aliskiren Does Not Protect the Heart from the Acute Histopathological Effects of Fat Embolism when it Protects the Lungs
Authors: Ponnapureddy Rakesh , Poisner Alan , Fletcher Amanda , Patel Chirag , Tappeta Kathyayini , Fotouhi Ariana , Molteni Agostino
Published: November 2023

Introduction

Fat embolism (FE) can lead to both acute and chronic lung injury. In an animal model of FE induced by Triolein, the histopathological damage was not limited to the lungs but also involved the heart and kidneys. We have previously demonstrated that losartan, an angiotensin receptor blocker, prevented the damage induced by FE in both the lungs and the heart at 10 weeks. We also identified significant pulmonary damage as early as 48 hours and it was prevented by the direct renin inhibitor, Aliskiren suggesting the role of Renin‐Angiotensin System (RAS) in the pathogenesis of fibrosis. In the current study we examined the acute effects of FE (48 hours) on the heart, the influence of Aliskiren on this organ and compared it to the effects on the lungs.

Methods

Twenty‐two rats were divided into controls (n=4, Group A) and three FE groups (n=6, Groups B, C & D). FE induction was done with Triolein 0.2 mL i.v. at 0 hours, and an hour later the animals received 0.2 ml i.p. saline (Groups A&B), Aliskiren at 50 mg/kg (Group C) or at 100 mg/kg (Group D). Rats were euthanized at 48 hours and hearts were fixed and stained with H&E for lumen patency measurements, Masson's Trichrome (MT) for collagen, and alpha‐smooth muscle actin (SMA) for myofibroblasts.

Results

Rats in FE only group (group B) had higher percentage of SMA staining around the branches of the coronary arteries compared to the control group (A) (P<0.05). There were no significant differences in lumen patency, media‐adventitia ratios and MT staining among the four groups. Aliskiren at both doses (C & D) did not show a significant effect on SMA staining compared to FE only (B). In contrast, Aliskiren at both doses showed reduction in SMA and MT staining in the Lungs.

Conclusion

Animals subjected to FE sustained acute injury (48 hours) of both the heart and the lungs, with less prominent changes in the heart. While Aliskiren significantly reduced the fibrotic damage in the lungs, such effect was not seen in the hearts of the same animals. This is in contrast to the delayed effects of FE at 10 weeks when there was similar extent of damage to both organs and protection by AT1 blocker losartan. These varying results suggest different pathophysiological processes in the evolution of the fibrosis in the two organs.

Support or Funding Information

Mary Katherine Geldmacher Research Foundation, St. Louis, MO
The Effects of Virally‐Induced Maternal Inflammation on the Methylation Patterns of Skeletal Muscle in Offspring
Authors: Hogan Elizabeth K. , Beever Jonathan E. , Dilger Anna C.
Published: November 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) infection during gestation is associated with increased cytokine expression and reduced muscle fiber development in the offspring of infected sows. As maternal environment can potentially alter DNA methylation patterns of progeny during development, the influence of virally‐induced maternal inflammation on the methylome of skeletal muscle in piglets was investigated. We propose that the changes in immune function and muscle development observed in the offspring of PRRSV‐infected sows are the result of epigenetic modifications in the progeny's genome. More specifically, we suggest that changes in the methylation patterns of the offspring's genome are associated with genes belonging to pathways regulating muscle growth and immune response. Pregnant pigs were inoculated with either PRRSV or sterile culture medium (CON) on approximately day 80 of gestation. At birth, longissimus dorsi muscle samples were collected from uninfected male offspring. Reduced representation bisulfite sequencing was used to determine methylation status of individual CpG sites throughout the genome. Differentially methylated CpG sites, defined as having at least a 25% (q<0.01) difference in methylation between treatments, were used in pathway and gene ontology analyses. Overall frequency of methylated CpG sites was virtually unchanged between PRRSV (46.36% of CpG sites methylated) and CON offspring (46.30%). Despite this, methylation patterns differed between treatments with 5593 cytosines from 717 genes hypermethylated and 566 cytosines from 262 genes hypomethylated in PRRSV piglets compared with CON piglets. Several genes were extremely hypermethylated in PRRSV piglets, including FcγRII, MEF2C, citrate synthase, and PRKAB2, and increased methylation was also observed in several disease response pathways, the thyroid hormone signaling pathway, and oxidative phosphorylation pathway. Differential methylation, mostly hypermethylation, was also present in genes for fast‐twitch myosin heavy chain isoforms, IGF1R, and several IGF binding proteins. Overall, these data suggest that differential methylation resulting from maternal infection and inflammation underlies reductions in offspring muscle development and growth.
Three‐dimensional Histochemistry and Imaging of Extracellular Matrix‐rich Human Tissues
Authors: Van Noorden Cornelis J.F.
Published: November 2023

For 3‐dimensional (3D) imaging of tissues, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1. clearing of the opaque tissue to render it transparent for microscopy, 2. fluorescence labeling of the tissues and 3. 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most of these clearing techniques are based on dissolving membranes and have been applied to the central nervous system and other tissues that contain relatively low amounts of extracellular matrix (ECM). Tissues containing large amounts of ECM such as dermis in skin and gingiva are difficult to clear in this way. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing ECM‐rich tissues. The principle of this type of clearing is that the entire tissue has one refractive index, that of BABB or DBE. We applied the BABB method in combination with immunofluorescence staining of CD31, an endothelial marker, and YOYO‐3, a fluorescent DNA dye, light‐sheet microscopy and Imaris‐based image analysis and processing to investigate the vasculature network in 3D in 12 human gingiva samples without signs of inflammation. 3D images showed the vascular network in 3D in the lamina propria of gingiva with loops into the papillae. The vascular network showed a high degree of tortuosity and irregularities in structure which are not apparent in images of sections of gingiva. This 3D histochemistry and imaging methodology is an excellent tool to study structural aspects of human gingiva that are involved in diseased periodontium.

Support or Funding Information

No funding.
Scientometric Analysis of Publications on Three‐dimensional Bioprinting
Authors: Sohn Eunsoo , Sohn Eun‐Hwa
Published: November 2023

Three‐dimensional (3D) printing has emerged as a disruptive technology for rapid prototyping and additive manufacturing. Bioprinting, the process of creating spatially controlled cell patterns with the use of 3D printers, has been developing personalized living tissues or artificial organs specific to each patient. Recent advances in bioprinting of tissues and organs has been driving new innovations in a variety of areas including tissue engineering and regenerative medicine, manufacturing, and biosciences such as biomedical research, transplantation and clinics, drug discovery and delivery. The aim of this study is to analyze the global scientific research output indexed in Web of Science database and estimate its R&D trend in the field of bioprinting through scientometric methods. Total 1,644 articles were retrieved and further analyzed. KnowledgeMatrix Plus, Gephi and VOSviewer software have been also used for analysis. Results showed that the R&D activivities on bioprinting have increased dramatically in recent years and major topics of this bioprinting field were identified. Recent advances in each nation's research activities and the international collaboration network in bioprinting have also been discussed.

Support or Funding Information

This research was supported by Korea Institute of Science and Technology Information under the program “Development of Technology Intelligence System for Exploring Future Technologies” from the Ministry of Science, ICT and Future Planning in Korea.
Biosafety Assessment of Petroleum Ether Oil of Ricinus communis C in Wistar Rats
Authors: Adenike Adeyemo Christy , Adeniyi Adedayo Francis , Adeniyi Adedotun Anthony
Published: November 2023

Objectives

The study was aimed at evaluating the biosafety of reported insecticidal potency of Ricinus communis petroleum extract (RCPE) used on stored products using wistar rats as a model.

Methodology

Ricinus communis seeds were extracted using soxhlet extractor and the filtrate later concentrated using the rotary evaporator to obtain R. communis petroleum ether extract (RCPE). Twenty four rats were divided into four groups labeled I, II, III and IV (six rats per group). Group I served as the control group and were administered orally with Dimethyl Sulphoxide (DMSO) and normal saline, Group II were administered orally with 500mg/kg of RCPE, Group III were administered orally with1000mg/kg of RCPE while Group IV were administered orally with 2000mg/kg of RCPE all dissolved in DMSO and Normal saline. Animals were weighed, anesthetized and blood samples were collected at the end 5 days of oral administration. Blood samples were collected by cardiac puncture for some biochemical parameters such as Total proteins, bilirubin, cholesterol, uric acid, creatinine, Urea and Uric acid activities as well as serum, AST and ALT were determined.

Results

At the end of this research work, it was discovered that at doses higher than 500mg/kg there were enzymatic leakages from the organs (kidney and liver) into the serum, compared to the control group.

Conclusion

The study revealed that it is advisable to use minimal dosages for the management of insect pest on products meant to be consumed by human, to prevent damage to vital organs as observed in the results at higher doses while higher doses should be for seeds meant for propagation.

Support or Funding Information

None
The Impact of Early Detection of Mental Illness in Jails and Prisons
Authors: Ekwe Benneth I , Einstein George P , Tulp Orien L
Published: November 2023

The research was concerned with discovering the impact of early detection of mental illness in prisons, using selected prisons across the five regions of the United States as case studies. Therefore, the research project set out with the following research questions: (a) What is psychological trauma, and how vulnerable are individuals who are experiencing an unwanted change of scene (from their homes to prisons) to becoming traumatic?, (b) Is the prison system equipped to detect mental illness among incoming inmates?, (c) What are the effects of the inability to detect mental illness among new prisoners on the prison?, (d) To what extent has the justice system contributed to mental illness of imprisoned individuals?, (e) To what extent can the actions of concerned reformed groups prevent the exacerbation of mental illness among incoming prison inmates?, and (f) What recommendations can be made to engender reformation of the prison system in order to bring about salutary benefits to the society, prison inmates, and prison administrators?. Consequently, relevant literatures were reviewed with respect to as the concept of mental illness, early signals of mental illness, symptoms and signs of mental illness and mental illness in prisons. A survey was carried out via the questionnaire method among ninety‐eight informed stakeholders in the prison system with the aim of providing solutions to the above broad research questions. Findings from the survey revealed that: (i) the American prison system is apparently not well equipped to detect mental illness among incoming inmates, (ii) the justice system contributed to mental illness among convicts, and (iii) advocacy and pressure groups have played a significant role in preventing the exacerbation of mental illness among incoming prison inmates. Thus, this study showed that the prison system must engender researches that will provide prison officers with needed technical, medical, and psychological tools for the early detecting of mental illness among incoming inmates at an early stage of their incarceration.

Support or Funding Information

Supported by Institutional Resources of USAT and Einstein Medical Institute
Validated Antibody Database (VAD): a database of antibodies curated from publications
Authors: Xie Hanqing
Published: November 2023

While antibodies used for therapeutics and clinical diagnosis are subject to stringent regulations by health authorities throughout the world, there are no standards or third‐party quality controls for research antibodies. Hundreds of biotech companies offer research antibodies, which are either polyclonal, monoclonal, or more recently, recombinant. However, the specificities of these antibody reagents do not always match scientists' expectations. An antibody might bind non‐specific targets and might not be suitable for a specific application. Utilization of such an antibody often leads to false positive results. These misleading results nullify important discoveries, discredit a research team and impede scientific progress. Academic journals have withdrawn articles presenting data based on non‐specific antibodies, and poor antibody quality has been attributed as one of the causes for the irreproducibility of published discoveries. In order to help alleviate this antibody quality and specificity problem, Labome organizes antibody applications cited in formal publications and has developed Validated Antibody Database (VAD). VAD, a manually curated database, compiles commercial and non‐commercial antibodies whose specificities and applications have been independently reported in published results from formal articles. Our curation priorities are articles with monoclonal antibodies and those discussing knockout studies. One of the benefits of our curation effort is the identification of cross‐reactive species and novel applications for antibodies, which are often developed for human/mouse proteins and tested by suppliers for a limited number of applications. Labome registers many antibodies having cross‐reactivities with model organisms such as flies, worms, zebrafish, and frogs and with novel applications from the literature. The current version was released in September 2016 and is freely accessible for online browsing.
Autonomic nervous tone during histopathological diagnosis of oral squamous cell carcinoma in virtual images
Authors: Mondragon Edward Acero
Published: November 2023

INTRODUCTION

By morphophysiological connections between autonomic nervous system or ANS with heart sinus node pacemarker cells, is documented activity of ANS by analysis of variability of heart frequence or HFV and cognitive events. The histopathologic diagnosis is a cognitive challenge by enormous integration of basic and clinical in a little time and that has his effect on ANS

OBJECTIVE

During cognitive task to build a diagnosis of oral squamous cell carcinoma or OSCC in virtual histological images exist an autonomic tone and this is different when diagnosis fail?

MATERIALS Y METHODS

Ten residents of surgery maxillo facial in his first year during postgraduate histology course were recruited to use a device and measure his HVF to extract off line his power spectral and to find sympathetic activitiy in band LF (0,04 –0,15Hz) and parasympathetic activity in HF (0,4–0,15Hz) during free interactions with OSCC virtual image until to make a diagnosis. The autonomic tone was calculated with the time predominant in any band during visual interaction.

RESULTS

Eight residents achieving diagnosis of OSCC in different times ×= 1,45s, SD=0,50s) of interaction with virtual images but with sympathetic autonomic tone in Gaussian distribution; while two residents with more time of virtual interaction (×= 2,23s, SD=0,31s) also with sympathetic tone his profile was incremental tone sympathetic with Gaussian distribution and who failed using more time and also had an autonomic tone sympathetic but incremental

CONCLUSION

Eight residents facial maxillofacial surgery in their first year achieving a cognitive task to diagnosis of oral squamous cell carcinoma or OSCC in virtual images, they have an autonomic nervous tone sympathetic with Gaussian distribution, and those who fail have used more time and also have a nervous tone sympathetic but of incremental distribution

Support or Funding Information

Doctorado en Educación. Universidad de Baja California. Tepic, Nayarit‐México
Role of Opioid‐Sensitive Descending Pain Modulatory Pathways in Affective and Sensory Components of Chronic Pain in Rats
Authors: Robles Dagoberto , Gomtsian Lusine , Navratilova Edita , Porreca Frank
Published: November 2023

Pain is a complex, multidimensional experience that is composed of sensory, affective and cognitive features. For unknown reasons, in some individuals, pain may become chronic. Unfortunately, there are no cures for chronic pain. Opioids remain one of the most important classes of drugs to treat pain but whether they are useful in chronic pain remains uncertain. Additionally, these drugs have significant side effects including tolerance, dependence and addiction. As a result, there is an urgent medical need to elucidate the underlining mechanisms by which relief of pain occurs. Opioids produce their effects primarily by alleviating the aversive qualities of pain. How this occurs is not known but pain aversiveness is thought to be integrated, in part, in the anterior cingulate cortex (ACC). Cortical regions in the brain likely contribute to context dependent modulation of the pain experience through projections that ultimately converge on the rostral ventromedial medulla (RVM). Here, we determined the effects of microinjection of morphine in several regions of the rat ACC in rats with chronic experimental neuropathic pain induced by ligation of the spinal nerve (SNL model). The possible effect of ACC or RVM morphine on mechanical hypersensitivity was evaluated using von Frey filaments. Microinjection of morphine into different sites of the ACC failed to reverse mechanical hypersensitivity in nerve‐injured animals. In contrast, morphine injection in the RVM reversed evoked thresholds in SNL animals. These findings suggest that morphine may differentially modulate affective dimensions of pain within the ACC without altering sensory components. The primary goal of this research is to understand the nature of the neuroanatomical contributions of the ACC and its role in descending pain modulatory pathways. Further studies exploring other sites within the ACC with measures of affective qualities of pain may ultimately lead to a better understanding of opioid‐sensitive circuitry.

Support or Funding Information

Supported by DA034975 from the NIH.
In vivo characterization of the novel delta opioid receptor positive allosteric modulator BMS‐986187
Authors: Dripps Isaac J , Boyer Brett , Traynor John , Jutkiewicz Emily
Published: November 2023

The delta opioid receptor (DOPr) is a member of the opioid receptor family of G protein‐coupled receptors (GPCR). Activation of DOPr induces antinociception, antihyperalgesia, and antidepressant‐like effects in animal models. However, some DOPr agonists cause convulsions, hindering their development as therapeutics in humans. Positive allosteric modulators (PAMs) bind to a receptor site distinct from the orthosteric binding site of a GPCR and may have several advantages over orthosteric agonists including greater selectivity, a larger safety margin and preservation of the spatiotemporal integrity of the endogenous system. Therefore, a PAM could be an effective strategy for eliciting DOPr‐mediated therapeutic effects without convulsions. To evaluate this hypothesis, we investigated the ability of the DOPr PAM BMS‐986187 to elicit DOPr‐mediated behaviors in mice alone or in combination with the DOPr orthosteric agonist SNC80. DOPr‐mediated antinociception was assessed in the acetic acid‐induced stretch assay. Antihyperalgesia was evaluated using a nitroglycerin‐induced thermal hyperalgesia assay. Antidepressant‐like effects were measured using the forced swim test. BMS‐986187 enhanced the potency of SNC80 to induce antinociception and antihyperalgesia without altering SNC80‐induced convulsions. BMS‐986187 alone produced antidepressant‐like effects without convulsions. These antidepressant‐like effects were blocked by the DOPr antagonist naltrindole and absent in DOPr knockout mice, indicating a DOPr‐mediated effect. Pretreatment with the enkephalinase inhibitor RB101 produced a synergistic effect in the forced swim test with BMS‐986187 but not SNC80 suggesting that BMS‐986187 exerts it antidepressant‐like effects by enhancing the actions of endogenous enkephalins. Overall, these findings suggest that BMS‐986187 functionally increases the therapeutic index of SNC80 and that a DOPr PAM could be a safer alternative to an orthosteric agonist as a novel treatment for depression.

Support or Funding Information

This project was partially funded by a PhRMA Foundation Starter Grant to EMJ and by NIH Grant DA035316 to JRT.
Novel synthetic opioids produce potent morphine‐like discriminative stimulus effects in rats
Authors: Korber Matthew Gerard , Chambers Christina , Walker Ellen
Published: November 2023

An increasing number of novel psychoactive substances have emerged over the past decade, several of which act on the opioid neurotransmission system. Recently, a series of compounds with fentanyl‐like structures appeared on the illicit drug market and have been responsible for fatalities. The purpose of the present study was to examine four novel synthetic opioids for their relative potency to the reference opioids morphine and fentanyl, and to characterize the relative susceptibility to naltrexone antagonism using drug discrimination. In animal models of substance abuse, drug discrimination techniques are useful due to the pharmacological selectivity and sensitivity to underlying mechanisms. Male, Sprague Dawley rats (n=11) were trained to discriminate between 3.2 mg/kg morphine, s.c. and saline in a two‐choice, drug discrimination procedure under a fixed ratio‐5 schedule to receive a sucrose pellet reward. Single trial training and testing were used to evaluate doses of saline, morphine, fentanyl, acetyl fentanyl, butyryl fentanyl, AH‐7921, and MT‐45. Rats learned the morphine vs. saline discrimination in 34 days (range 12–110 days). Fentanyl and all four synthetic opioids fully‐substituted for morphine in a dose dependent manner in all rats with the following rank order of potency: fentanyl>butyryl fentanyl>acetyl fentanyl>AH‐7921>MT45>morphine. Although all opioids were blocked by naltrexone, MT‐45 and AH‐7921 appeared especially sensitive to naltrexone antagonism. Butyryl fentanyl was the least sensitive to naltrexone antagonism. In conclusion, the synthetic opioids were significantly more potent than morphine but nevertheless less potent than fentanyl and sensitive to naltrexone antagonism suggesting that these compounds have a similar abuse liability as either fentanyl or morphine.

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(Support by Department of Justice, DJD‐15‐ HQ‐P‐ 0740)
Exploring the pharmacologic and discriminative effects of abused psychostimulants and the bath salt component mephedrone in rats
Authors: Milewski Andrew J , Rawls Scott , Walker Ellen A , Saber Iman
Published: November 2023

The underlying mechanisms of both commonly abused and novel psychostimulants such as mephedrone are still a critical area of study. Comparing mephedrone to other more well‐known drugs in an established drug discrimination protocol allows for increased understanding of their pharmacological profiles and potential abuse liabilities. We hypothesize that mephedrone exhibits mixed pharmacology with low doses having a primarily serotonergic mechanism, and higher doses having a primarily dopaminergic mechanism. Male Sprague‐Dawley rats were trained using two‐choice drug discrimination assays to examine the stimulus properties of either a low dose of 0.5 mg/kg mephedrone (n=12) vs saline or a high dose of 3.2 mg/kg mephedrone vs saline (n=11). Rats learned the low and high dose discriminations in 74 and 175 sessions, respectively. Current results show that mephedrone substitutes in a dose‐dependent fashion in both groups, although with different potencies. In the low dose cohort, dopamine (DA) agonists (cocaine and D‐amphetamine) partially substitute for mephedrone whereas methamphetamine fully substitutes. However, we did not see full substitution of the aforementioned DA agonists in the high mephedrone training dose group. The serotonergic agonist (2,5‐Dimethoxy‐4‐iodoamphetamine or DOI) in moderate to high doses (0.5 to 1.0 mg/kg) partially substituted for both high and low doses of mephedrone. In conclusion, mephedrone appears to mimic pharmacological properties similar to other psychostimulants that possess dual DA and 5‐HT mechanisms and the high dose mephedrone training dose cohort may be less sensitive to DA activation than the low dose cohort. Further analysis will focus more on the susceptibility of mephedrone to DA and 5‐HT antagonism.

Support or Funding Information

Supported by R21DA032718
Lorcaserin decreases the reinforcing effects of 3,4‐methylenedioxypyrovalerone (MDPV) and cocaine in Sprague‐Dawley rats
Authors: Gannon Brenda M , Rice Kenner C , Collins Gregory T
Published: November 2023

Lorcaserin is a serotonin (5‐HT) 2C receptor‐preferring agonist that is currently approved by the Food and Drug Administration to treat obesity; however, its behavioral effects are also mediated by 5‐HT 2A and 1A receptors. Agonists acting at 5‐HT2C receptors are known to dampen dopamine neurotransmission, an effect that could be beneficial for treating drug abuse. 3,4‐Methylenedioxypyrovalerone (MDPV) is a cocaine‐like monoamine reuptake inhibitor that is commonly found in abused bath salt preparations. Recent studies have demonstrated lorcaserin decreases the reinforcing effects of cocaine in rats and monkeys, and the present study aimed to: (1) determine whether lorcaserin was equally effective at decreasing the reinforcing effects of MDPV and cocaine; and (2) determine the receptor(s) responsible for the effects of lorcaserin on cocaine and MDPV self‐administration. Male Sprague‐Dawley rats (n=6) were injected with lorcaserin (0.1–5.6 mg/kg, IP) 25 minutes before the initiation of MDPV or cocaine self‐administration sessions. Lorcaserin was equipotent at suppressing responding for MDPV and cocaine; however, individual differences in sensitivity to lorcaserin were observed. To determine which receptor mediated the effects of lorcaserin, rats were administered 5‐HT1A (WAY100635, 0.178 mg/kg), 5‐HT2A (MDL100907, 0.1 mg/kg), or 5‐HT2C (SB242084, 0.1 mg/kg) receptor antagonists (IP) 15 minutes prior to lorcaserin treatment. Antagonism of 5‐HT2C (but not 5‐HT1A or 5‐HT2A) receptors reversed the effects of lorcaserin on MDPV and cocaine self‐administration. Taken together, these data indicate lorcaserin may be an effective pharmacotherapy against MDPV and cocaine abuse through its agonist actions at 5‐HT2C receptors.

Support or Funding Information

This research was supported by the National Institutes of Health (NIH) and the National Institute on Drug Abuse (NIDA) R01DA039146 (GTC) and T32DA031115 and the NIH Intramural Research Programs of the NIDA and the National Institute of Alcohol Abuse and Alcoholism (NIAAA) (KCR).
GABAA Negative Modulation Selectively Attenuates Cocaine Self‐Administration In Rats
Authors: Nicholson Katherine L , Shelton Keith L
Published: November 2023

GABAA receptors are critical to normal CNS functioning, abundant in brain areas involved in motivational processes and have been implicated in neurological disorders including substance use disorders. Modulation of GABAA receptors can alter the effects of abused drugs including those which do not directly interact with GABAA receptors. Our previous data showed that a low efficacy benzodiazepine‐site negative GABAA modulator will attenuate both toluene and methamphetamine‐facilitated intracranial self‐stimulation in mice and attenuate methamphetamine‐stimulated extracellular dopamine levels in the nucleus accumbens of mice in vivo. Given the critical placement of GABAA receptor populations within dopaminergic drug reward pathways, the current study investigated the hypothesis that negative allosteric modulation of GABAA receptors selectively alters reward circuitry to reduce the abuse‐related effects of cocaine. The effects of the negative GABAA modulator Ro 15,4513 on cocaine self‐administration was examined in adult male Sprague‐Dawley rats. Two groups of rats were trained on a fixed‐ratio 5 (FR5) schedule to self‐administer intravenous injections of 0.1 or 0.3 mg/kg/infusion cocaine in daily 2‐hr sessions. To further assess the selectivity of GABAA negative modulation for altering cocaine's effects, a third group of rats was trained to respond under a FR5 schedule for 45‐mg food pellets. After reaching stable levels of performance the rats were pretreated with vehicle, 0.3, 1 or 3 mg/kg intraperitoneal Ro15‐4513 prior to the 2‐hr operant test sessions. Each test session was separated by at least 3 days of training to allow Ro 15‐4313 washout and reestablish stable baseline rates of lever pressing behavior. Ro15‐4513 dose‐dependently attenuated cocaine self‐administration at both the 0.1 and 0.3 mg/kg/infusion cocaine self‐administration doses with responding almost completely eliminated by 3 mg/kg Ro 15‐4513. In contrast, the same doses of Ro15‐4513 had minimal effects on rates of food reinforced lever‐pressing. These data demonstrate that negative GABAA receptor modulation will attenuate intravenous cocaine self‐administration in male rats at doses that do not impact food‐maintained performance. Overall, our studies and prior data suggest negative modulation of the benzodiazepine‐site on GABAA receptors may be a promising pathway for the development of novel broad spectrum pharmacotherapeutics for substance abuse treatment.