bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing on line and live versions of an Anatomic Radiology Clerkship
Authors: Stern Richard H , Simpson William , Laitman Jeffrey T
Published: June 2021

We report our experience with a required 4th year Anatomic Radiology clerkship started in 2005 at the Mount Sinai School of Medicine (140 students/yr). A significant problem both from student perspective and administration has been the students’ need to be away from MSSM in the fall of the 4th year due to away “audition” electives or residency interviews requiring absence. To overcome this, an online option for the clerkship (ARO) was started in 2009. Students could take the clerkship away from Mount Sinai with an internet connection. Students review seven modules, each with an “unknown” case. Students evaluate the case and answer a series of MCQ questions. In addition, there is an online MCQ exam. The overall grade for ARO is 40% / exam and 60% / composite grade of the unknown cases. The in‐class (“live”) version of the clerkship (ARL) consists of two weeks of interactive lectures and case presentation. Grades consist of a MCQ final, oral and written case presentation and class participation. Student feedback has shown that while the ARO is much appreciated, ARL has had a consistently higher student approval rating than ARO, indeed being amongst the highest rated of Clerkship experiences.
Comparison of the efficacy of popular weight loss programs in sedentary overweight women IV: bone, protein & liver status
Authors: Galvan E , Baetge C , Lockard B , Mardock M , Simbo S , Jung Y , Levers K , Byrd M , Koozehchian M , Khanna D , Sanchez B , Jagim A , Oliver J , Kresta J , Horrell K , Leopold T , Cho M , Rasmussen C , Kreider R
Published: June 2021

126 sedentary women (44±12 yr, 44.8±5% body fat, 35.4±6 kg/m2) were randomized to participate in a non‐exercise and no diet control group (C) or the Curves Complete® 90‐day Challenge (CC), Weight Watchers® Points Plus (WW), Jenny Craig® (JC), or Nutrisystem® Advance Select™ (NS) weight loss programs for 12‐wks. Fasting blood samples were obtained at 0, 4, 8, and 12 wks and analyzed by MANOVA. No significant interactions were observed among control and diet groups in bone mineral area (p=0.79), bone mineral content (p=0.41), bone mineral density (p=0.39), serum calcium (p=0.60), alkaline phosphate (p=0.39), total protein (p=0.22), blood urea nitrogen (p=0.41), creatinine (p=0.20), BUN/Creatinine ratio (p=0.31), aspartate amino‐transaminase (p=0.51), alanine amino‐transaminase (p=0.37), total bilirubin (p=0.41), albumin (p=0.30), globulin (p=0.18), or albumin/globulin ratio (p=0.65). Changes in these bone markers did not significantly correlate to changes in protein status or liver function. Results indicate that participation in these popular diets does not negatively affect bone status, markers of protein, or liver function. Supported by Curves International (Waco, TX)
Combining radiology technicians and medical students to develop imaging and interpretation skills
Authors: Aabo Megan , Delamarter Taylor , Benninger Brion
Published: June 2021

INTRODUCTION

First year medical students (MS1) are generally introduced to radiology during their anatomy course with a brief overview and limited roentograph teaching. Imaging interpretation skills could be taught during the anatomy dissection lab (ADL). In a vertical curriculum, it is essential to integrate basic and clinical sciences to enable MS1 to confidently apply critical thinking skills. The objective of this study was to combine MS1 with radiology technicians (RTs) during ADL to develop and improve MS1 imaging and interprtation skills.

METHODS

Literature search was conducted on combining MS1 and RTs during ADL. Exam scores were analyzed and a questionnaire was conducted for assessment.

RESULTS

Literature search revealed no studies combing MS1 and RTs during ADL course. Exams and a questionnaire revealed both an objective and perceptual success.

DISCUSSION

An interprofessional educational model was designed to expose MS1 to various radiologic mediums that focused on fundamentals of capturing desired images. RT's taught MS1 the how, what, where and why to capture and interpret imaging. Exam scores were high and a questionnaire suggested this novel model an educational success.

CONCLUSION

This pilot study introduced a novel interprofessional education model to develop and improve imaging knowledge during an anatomy course within a vertical curriculum.
A double blind placebo controlled clinical trial evaluating the effects of LPT3‐04 on body weight & composition in overweight & mildly obese healthy adults
Authors: Kalman Douglas , Feldman Samantha
Published: June 2021

In a 12 wk RDBPCT, 32 healthy overweight/obese adults (43.5±11.6y.o; 29.33±2.52mg/m2) were allotted to either the LPT3‐04 or Placebo (n=16 per group). Over the 12‐weeks of the study, tests were standardized at baseline & weeks 4, 8 & 12. The tests of interest included body weight, composition & safety markers. All subjects were instructed on caloric intake (RMRx1.3 AF ‐ 500) coupled with a 5d/wk exercise program of moderate intensity for 30 min/session & compliance assessed via dichotomous questionnaires. Body weight was measured in minimal essential clothing on a calibrated digital scale, while body composition was measured by DEXA. Safety markers included CMP, CBC w/differential, vitals, AE's & subjective remarks over the 12/wk period. Weight loss was significantly different between the groups, favoring the LPT group (LPT −3.01±2.32kg vs. Pla −1.65±2.55kg; p=0.037). Change in % body fat did not differ between the groups, both groups lost significant amount of fat mass (LPT −4.06±4.51kg p=0.005 & Pla −3.61±3.97 kg p=0.013). There was a borderline significant difference for change in fat free mass (LPT −2.29±3.12kg vs. Pla 0.192.77kg; p=0.051). There were no SAE's or difference in AE's between the groups, nor any clinically significant changes in lab values observed. The results of this study support a weight loss effect for LPT, the active group lost significantly more weight than the placebo.
Mixed vegetables and fruits ferment modulate the immune system in OVA‐induced mice
Authors: Yang Jo-Hsuan , Tsai Jyun-Han , Chao Huan-chun , Huang Hui-Yu
Published: June 2021

Mix Vegetables and fruits fermented drinks (Fu Gui, FG‐enzyme) have long been used as food substance in Asia. FG‐enzyme is rich with vitamins, minerals, varieties of monosaccharides and antioxidants. This study investigated FG‐enzyme effect on immune modulation in OVA‐induced BALB/c mice. Thirty mice were divided into three groups, including control, single dose and triple dose groups. The immune modulation effects of FG‐enzyme were determined by assaying the cytokine secretion, splenocytes subsets populations, natural killer cell (NK cell) activity and phagocytosis. Results showed that FG‐enzyme elevate the T cell proliferation with single and triple doses in the cultured splenocytes of OVA‐induced mice compared to control. Determined phagocytosis capacity in the blood, and NK cell activity in splenocytes were found to increase only with single dose. In addition, we found increased the cytokines such as interleukin‐2, (IL‐2) and IL‐4 concentrations with single and triple doses in both ConA and OVA‐induced mice, while IL‐5 was increased only in ConA mice. Nevertheless, IL‐10 and interferon‐£^ (IFN‐£^) concentrations were increased in both ConA and OVA‐mice with triple dose only. Results from our study conclude that FG‐enzyme is able to modulate the immune system in OVA‐induced mice with subsequent maintenance of inflammatory cytokines and phagocytosis.
Novel Anorexia Nervosa Refeeding Strategies: From Human to Rat and Back Again
Authors: Higgins Janine , MacLaean Paul , Giles Erin , Moore Rachel , Kasten Melanie , Pan Zhaoxing , Hagman Jennifer
Published: June 2021

Aims

1) To define changes in diet and physical activity (PA) that lead to inpatient treatment of anorexia nervosa (AN). 2) To use this data to refine a rat model of AN and examine the effects of a novel refeeding diet.

Methods

1) 15 females, 12–18 years, completed a FFQ, 24h diet recall, Pediatric PA Recall, and Modifiable Activity Questionnaire to assess changes in diet and the PA that lead to inpatient admission. 2) AN was induced in rats via free access to a running wheel and 1h access to low fat (LF) diet per day. Rats were re‐fed either LF (15% fat, 15% protein; AN LF) or test (30% fat, 28% protein, 1% leucine; AN moderate fat, AN MF) diet. Controls (C) were identical to AN LF but with no access to a running wheel (no AN). Body fat (BF) was assessed by QMR and fat pad weights. Energy balance was measured via indirect calorimetry.

Results

1) PA increased 300% prior to inpatient admission without any change in energy or macronutrient intake. 2) AN LF recovered 100% of initial weight after 7d of refeeding (8% BF) whereas AN MF did not return to 100% weight (4% BF) due to a 50% decrease in energy intake in AN MF vs AN LF with no difference in total energy expenditure. AN LF rats had fatty liver and higher visceral fat content than both C and AN MF.

Conclusions

1) Increased PA, not decreased energy intake, precipitated hospitalization for AN. 2) MF is not a dietary treatment for AN. However, LF diet causes fatty liver and visceral fat accumulation.
Overall and abdominal adiposity and risk of hypertriglyceridemia among Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2008
Authors: Lee Hye-Seung Heather , Lee Hae Jeung , Cho Jang-Ik , Stampfer Meir J , Willett Walter c , Kim Cho-il , Cho Eunyoung
Published: June 2021

We examined whether overall obesity (body mass index, BMI) and abdominal obesity (waist circumference, WC) are independently associated with the risk of hypertriglyceridemia (HG) among the Korean population. A national sample of 5,036 Koreans aged 19–64 was examined with cross‐sectional surveys, the Korea National Health and Nutrition Examination Survey (KNHANES), in 2007 and 2008. BMI, WC, and other life‐style information were assessed. We documented 1,344 cases (26.7%) of HG (fasting triglycerides of >150mg/dl). Both BMI and WC were each independently associated with the risk of HG. Multivariate ORs of increasing categories of BMI (<18.5, 18.5≤ – <23, 23≤ – < 25, 25≤ – <28, ≥28 kg/m2), were 0.49, 1.00 (reference), 1.26, 1.63, and 1.84, respectively (p= 0.0007) adjusting for WC. WC was also positively associated with risk of HG across increasing quintiles of WC (multivariate‐adjusted ORs: 1.00 (reference), 1.54, 2.54, 2.21, and 2.36; p <0.0001), adjusting for BMI. The joint relation between BMI and WC and risk of HG showed that within each BMI category, higher WC predicted a greater risk of HG (p <0.0001). The ROC curves indicated that BMI (0.69) and WC (0.72) were similar in predicting HG. In conclusion, both BMI and WC were strongly independently associated with risk of HG among this Korean population. Both measurements should be used for assessing health risk in clinical settings and epidemiologic research among Asian population.
Luminal Leptin Impairs Intestinal Tight Junction Function in vitro through JAK2‐dependent Signaling Pathway
Authors: Kim Choon Young , Kim Kee-Hong
Published: June 2021

Tight junction (TJ) integrity is a critical for maintaining intestinal barrier function and inflammation. Obesity is also known to alter intestinal function partly through an impairment of intestine TJ integrity. Leptin is associated with inflammation and obesity. However, the role of leptin in TJ function is unknown. This study aimed to investigate the effect of leptin on intestinal TJ integrity in vitro using Caco‐2 BBe cells. Leptin addition to apical compartment, but not in basolateral compartment, caused TJ barrier dysfunction as judged by transepithelial electrical resistance and dextran fluxes. TJ dysfunction by luminal leptin was associated with reduced levels of gene expression related to TJ‐associated proteins, zonula occludens‐3, claudin‐5, and occludin. In addition, leptin treatment caused reduction in total protein level of occludin. Moreover, activation of the Janus family of tyrosine kinase/signal transducer and activator of transcription (JAK2/STAT3) axis has been also observed upon leptin treatment. Conversely, a JAK2 specific inhibitor or a PI3K specific inhibitor pretreatment abolished leptin activity on TJ integrity, indicating an involvement of JAK2 and PI3K signaling pathways in leptin‐impaired TJ function. Therefore, our results reveal previously unknown function of luminal leptin, which potentially links between obesity and its associated intestinal TJ dysfunction.
Inhibitory effects of Lactobacillus sakei proBio 65 on atopic dermatitis
Authors: KIM JI YUN , Rhee Dong-kwon , Pyo Suhkneung
Published: June 2021

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which is marked by elevated levels of IgE. Probiotics such as lactobacilli and bifidobacteria have been known to modulate immune responses and have been suggested as a potential treatment for allergies, but the effect of L. sakei proBio65 isolated from Kimchi has remained unexploited. In this study, we investigate the inhibitory effect of L. sakei proBio65 on allergic responses in vivo and in vitro. In NC/Nga mouse model, our result demonstrated that oral administration of L. sakei proBio65 improved skin condition and reduced scratching frequency. In addition, ELISA assay revealed that the levels of serum immunoglobulin E (IgE) and interleukin‐4 (IL‐4) was suppressed by L. sakei proBio65 treatment. The present data also showed that L. sakei proBio65 inhibited IgE‐mediated histamine and β‐hexosaminidase release from RBL‐2H3 cells. Taken together, these results suggest that L. sakei proBio65 has an inhibitory effect on atopic dermatitis (AD)‐like skin lesion and is proposed as an effective new anti‐inflammatory agent.
The effect of losartan on vasomotor dysfunction induced by hypercholesterolemia
Authors: Yilmaz Cigdem Erkuran , Yilmaz Gokhan
Published: June 2021

Angiotensin II type 1 receptor (AT1R) activation has been implicated in the endothelial dysfunction associated with hypercholesterolemia. Although inhibition of the Renin‐angiotensin system has been demonstrated to reduce atherosclerosis, the effect of AT1R blockade on the endothelium‐dependent dysfunction induced by hypercholesterolemia has not been documented widely. Our objective was to test that losartan, an AT1R blocker, would reverse the endothelium‐dependent vasomotor dysfunction induced by hypercholesterolemia in mice. C57BL/6 male mice fed on either with normal (ND) or high cholesterolemic diet (HCD) for 21 days, another group of HCD mice treated with losartan (HCD+LOS) (25 mg/kg per day) for the last 10 days of HCD. The endothelium‐dependent vasodilation was tested using ex vivo wire myography. Endothelium‐dependent vasodilation was assessed as % relaxation to 10−6 M acetylcholine at aortas precontracted with 10−6 M phenylephrine. Endothelium‐dependent vasodilation was impaired in HCD group (ND %69.2±11.3 vs HCD %11.3±7.6, P< 0.01 one‐way ANOVA). Losartan treatment abolished the impaired endothelial vasodilation in HCD group (LOS+HCD% 51.3±7.6 vs HCD %11.3±7.6, , P< 0.01). Since losartan is widely used clinically our findings might indicate an alternative therapeutic avenue for this drug in the treatment of hypercholesterolemia induced endothelial dysfunction.
Uropathogens from Qatari Type 2 diabetics with Asymptomatic Bacteruria
Authors: Afifi Nahla M , Abdullah Asmaa Abdullatef Abu , Albardawil Haneenn Moee , Yasin Heba Rashid , Rouban Wazeera Khaled , Ewis Soliman A
Published: June 2021

The urinary tract infections (UTIs) are among the most common bacterial infections in diabetic patients, especially asymptomatic bacteriuria. The aim of this study is to investigate the causative organisms of ABU in type 2 diabetic patients, the phylogenetic grouping and the antibiotic sensitivity pattern of the causative organism in order to determine the drug of choice to cure ASB in diabetics. Hundred – sixty eight men were recruited from attendance of the out patients clinics at the Army Force Medical Unit in Qatar and twere divided into two groups; Group 1 (130 type 2 diabetics) and Group 2 (38 non‐diabetic subjects). We found that 20% of diabetic patients had ASB and Escherichia coli were the most prevalent pathogen (92.31%). Genotypic study showed that the most prevalent E. coli groups responsible for UTI were belong to group A and B2 (33.3% for each group). Moreover, Nitrofurantoin was the most sensitive antibiotic for the groups B2, B1, D (100%) and 75% for group A. Phenotypic study by SEM showed that there is variation in the diameter, B1 group had the largest width and length (L= 2.391 ± 0.483)(W=622.667 ± 51.215) while group D was the shortest (L=1.876 ± 0.247) and group A had the lowest width (W=580.21 ± 44.93). Further comparing of virulence factors with symptomatic diabetics is required to determine why ASB lacked symptoms in spite the presence of virulence genes.
Erythropoietin induces myelin genes and the early growth factor 2 in oligodendrocytes through the classical erythropoietin receptor
Authors: Cervellini Ilaria , Annenkov Alexander , Chernajovsky Yuti , Ghezzi Pietro , Mengozzi Manuela
Published: June 2021

Erythropoietin (EPO), a cytokine involved in erythropoiesis, is also neuroprotective in vitro and in vivo. EPO reduces disease severity in multiple sclerosis, an autoimmune‐inflammatory disease that causes demyelination. Immunomodulatory agents can delay the course of the disease, but nothing is available for remyelination.

Despite EPO regulates erythropoiesis by the homodimeric EPO receptor (EPOR)2, variants of EPO not binding (EPOR)2 are still neuroprotective, so another receptor may be involved.

This study investigated the role of EPO in myelination and the receptors involved. CG4 cells, a rat oligodedrocyte progenitor cell line able to differentiate to oligodendrocytes, were used. There was no effect of EPO on myelin gene modulation in CG4 wild type cells, lacking of EPOR. However, in CG4 cells modified to overexpress EPOR, EPO increased myelin genes in a receptor dependent manner. In addition, the early growth response gene EGR2, involved in peripheral myelination, was expressed in these cells and increased by EPO treatment.

The correlation between EGR2 and myelin genes in oligodendrocytes, under investigation, could be a new finding in the study of central myelination. Greater understanding of the effect of EPO on myelination and the mechanism involved will help looking for therapies promoting remyelination.

Supported by BSMS and the European Regional Development Fund, TC2N
Development of molecular pathology tests for allelic variation in the serotonin transport gene
Authors: Reyes Marie , Kilpatrick Kathleen , Bearer Elaine
Published: June 2021

Post traumatic stress disorder (PTSD) is an anxiety disorder that occurs after a life‐threatening event in susceptible people. PTSD is characterized by persistent re‐experiencing the event, avoidance/numbing, and persistent arousal, resulting in severe loss of normal social functioning and often gives rise to co‐morbidity of other disorders. Some with PTSD experience relief from drugs that block the serotonin reuptake, implicating the serotonin transporter (SERT) in this disorder. Human populations have several variants of the SERT gene, primarily a long (L) and short (S) form of the promoter that modulate the amount of SERT expressed. We are developing a molecular pathology test to detect these alleles that can then be correlated with PTSD incidence, response to SSRI drugs, and relationship to structural changes in the brain. We are developing a PCR‐based test using DNA from ARPE19 cell line and primers that flank the promoter region (Mellman et Al. 1996, Gerlernter et Al. 1993). Nested primers and sequencing confirmed the specificity of this test for allelic variation in the promoter of the SERT gene in human chromosomes. We next plan to apply this test to human combat veterans with and without PTSD to determine the distribution of these alleles and correlate their presence with the clinical disorder. We expect that PTSD has several different underlying susceptibilities and SERT variation may not be 100% concordant.
Immunohistochemical examination of renal neovascularization in ischemia
Authors: Baderca Flavia , Zahoi Delia Elena , Daescu Ecaterina , Alexa Aurora
Published: June 2021

Neovascularization represents an important physiological response in ischemia. Renal neovascularization was already demonstrated in hypercholesterolemia. Probably, the trigger was ischemia as result of renal vasoconstriction. Renal neovascularization in primitive stages of atherosclerosis could be determinate by inflammation, an important mediator of angiogenesis. The study was retrospective, using kidneys samples taken at autopsy from 56 patients. Sections were stained with haematoxylin‐eosin method and immunohistochemically for CD31, CD34 and VEGF. With endothelial antibodies, the neovascularization was demonstrated by the presence of newly formed endothelial tubes originated from the endothelial cells of the veins’ luminal surface. They seep through the venous wall, from intima to adventicial tissue. These vascular elements were localized at venous‐tubular interface, parallel to adjacent collector ducts. At the same level, all cases presented an intense immunoreaction for VEGF in the cells lining the collecting ducts. In conclusion, the source of renal neovascularization was represented in the most cases by the adventicial blood vessels, but in the presence of ischemia the new formed blood vessels originated from luminal endothelial cells. More, the site of neovascularization was correlated with the expression of VEGF.
Anti‐amnesic effect of bioflavonoid and amino acid from Cnestis ferruginea in Mice
Authors: ishola ismaila O , Tota Santoshkumar , Adeyemi olufunmilayo O , Agbaje Esther O , Narender Tadigullopula , Shukla Rakesh
Published: June 2021

Introduction

Brain aging is characterized by cognitive decline and memory deficits that could be the result of oxidative stress and impaired cholinergic function. Cnestis ferruginea (Connaraceae) is a shrub widely used in traditional African Medicine for the treatment of various painful and inflammatory conditions.

Objective

This study was carried out to investigate the effect of methanolic root extract of Cnestis ferruginea (CF) and its active constituents on scopolamine (3mg/kg, IP) induced memory impairment in mice.

Methods

Memory function was evaluated by Morris water maze and passive avoidance tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioural studies.

Result

Administration of CF (25–200mg/kg, PO) for three days inhibited acetylcholinesterase (AChE) activity in the brain and prevented scopolamine induced memory impairment in mice (p<0.05). Further, through activity guided assay CF‐2 and CF‐5 were isolated from CF. CF‐2 and CF‐5 (12.5 and 25 mg/kg, PO), administered for 3 days, ameliorated memory impairment induced by scopolamine in Morris water maze and passive avoidance tests (p<0.001). Further, CF‐2 and CF‐5 produced significant (p<0.05) inhibition of AChE activity in mice brain far better than tacrine (5 mg/kg, PO). The crude extract and its active constituents exhibited antioxidant effect as shown by significant (p<0.05) decrease in MDA level and elevated GSH level in mice brain.

Conclusion

This study shows that CF‐2 and CF‐5 could be a novel drug in the management of dementia due to their potent antioxidant and AChE activity.
Aerosol delivery systems of siRNA for the treatment of lung cancer
Authors: Sung Meesook , Chung Hesson , Chan Hak-Kim
Published: June 2021

The project objective is to develop aerosol systems for delivery of siRNA to treat lung cancer. Specifically, we will (i) deliver siRNA to lung cancer cells in vivo, and (ii) evaluate the efficacy of siRNA delivery by observing lung cancer cells expressing green fluorescence proteins (GFP). The inhalation aerosol liposome was made with weakly positively charged (zeta potential 5–10 mv) and aerosol particle size (20 ~50 μm) using MicroSprayer(R)Aerolizer– ModelIA‐1C and FMJ‐250High Pressure Syringe. The mouse animal model bearing solid tumor in the lung was established by inoculation with B16F10‐GFP lung epithelial cells 3 weeks later. The aerosol delivery systems encapsulating Alexa555‐siRNA (negative control) and GFP‐siRNA are now evaluating for the encapsulating efficiency and stability. The delivery efficiency will be measured by decreasing the intensity of green fluorescence protein. This project is supported by New South Wales, Austria and Gangwon South Korea Technology Collaboration Grant.
Ebp50: A Novel Biomarker for Resistance to Endocrine and HER‐2 Targeted Therapies in Breast Cancer
Authors: gu Guowei , Covington Kyle Richard , Fernandez Natalie Michelle , Andoˈ Sebastiano , Fuqua Suzanne A.W.
Published: June 2021

Backgroud

EBP50 functions as a molecular scaffold to coordinate ion transport and second messenger signal transduciton. Recently, a number of studies suggest a role for EBP50 expression in cancer progression.

Methods

Microarray profiling. Stable transfection. Soft agar and MTT growth assays. Immunoblot and immunoprecipitation assays. Confocal microscopy.

Results

The mean levels of EBP50 were reduced in the tamoxifen (Tam) ‐resistant, metastatic breast tumors compared to Tam‐sensitive tumors. Knockdown of EBP50 decreased Tam sensitivity in MCF‐7 and ZR75B cells. EBP50 knockdown cells showed higher levels of phosphorylated HER2 and EGFR, as well as their downstream signalling pathways. PI3K/AKT inhibitors were able to restore Tam sensitivity in knockdown cells. Similarly, knockdown EBP50 in ERα/HER2 positive BT‐474 cells increased costitutive pHER2 and these cells were resistant not only to Tam, but also to Trastuzumab (Tras) treatment. EGFR inhibitor or Lapatinib were able to restore Tras sensitivity. We demonstrate that EBP50 is capable of binding to HER2 using immunoprecipitation and confocal microscopes, suggesting that EBP50 interacts directly with HER2. Our data suggest that EBP50 is a novel negative regulator of HER2 signaling, and its loss conferred resistance to both Tam and Tras. We hypothesize that EBP50 levels might be a new predictive biomarker for targeted therapy.
Scopoletin induces melanogenesis through CREB/PKA and p38 MAPK signaling pathway
Authors: Mun Yeun-Ja , Kim Dae-Sung , Lee Young-Eun , Woo Won-Hong
Published: June 2021

In this study, we investigated the molecular events of melanogenesis induced by scopoletin in B16 melanoma cells. To evaluate melanin relative expression, using RT‐PCR and western blotting, B16 cells were incubated for 24 h with scopoletin. Scopoletin induced the expression of tyrosinase, TRP1 and MITF proteins. Moreover, it increased the phosphorylation ERK, CREB and p38 MAPK. Scopoletin‐induced melanogenesis was reduced by H‐89, KT5720, PKA inhibitors, or SB203580, a p38 MAPK inhibitor, but not by Ro 320432, a PKC inhibitor, which suggests the involvement of PKA and p38 MAPK in scopoletin induced melanogenesis. Scopoletin induced the activation of CRE, which suggests that scopoletin‐induced melanogenesis is mediated by PKA, which occurs downstream of scopoletin‐increased cAMP production. This result was further confirmed by the fact that scopoletin‐induced phosphorylation of CREB was inhibited by H‐89, but not by PD98059, a MEK1 inhibitor. These results demonstrate that scopoletin induces melanogenesis through CREB/PKA and p38 MAPK signaling pathway.
Fabrication and characteristic of Curcumin‐loaded Poly(lactic acid) nanofiber mat and its potential use as wound healing materials
Authors: Ghosh Chiranjit , Nguyen Thuy Thi Thu , Park Jun Seo , Hwang Seong- Gu
Published: June 2021

Curcumin (Cur), extracted from the Curcuma longa L. plant, is well known for its anti–tumor, anti–oxidant, anti–inflammatory, anti–bacterial, wound healing and anti–scaring properties. A Cur–loaded poly(lactic acid) (PLA) nanofiber mat were obtained by electrospining a mixture of PLA and Cur solution in blend of chloroform and DMAc solvent. Field Emission Scanning Electron microscopy (FE–SEM) images showed a smooth morphology of resulted fibers with diameter in range of 300 and 500 nm. Herein, using the PLA nanofibers as a support and carrier for Cur could give rise to a large surface area that could improve the capability of treatment of Cur loaded. The potential use of cur‐loaded PLA nanofiber mat as wound healing materials was evaluated by 3T3‐L1 cell proliferation and attachment on the nanofiber mat. The cell viability slightly increased from 1 to 3 days and significantly increased in 5 days, indicating that the Cur‐loaded PLA nanofibers are non‐toxic to 3T3‐L1 cells. SEM observation showed the cells could spread and partly enmesh under fibers layer. In particularly, we observed faster wound closure of punch wounds in curcumin‐treated animals in comparison with untreated controls, suggesting that the PLA/Cur nanofibers could be a promising candidate to be used as wound healing materials.
Treatment with Cromolyn Sodium at early reperfusion but not before ischemia attenuates intestinal ischemia/reperfusion induced lung injury in mice
Authors: Gan Xiaoliang , Luo Chenfang , Luo Gangjian , Li Shangrong , Hei Ziqing , Xia Zhengyuan
Published: June 2021

Mast cell degranulation plays a key role in small intestinal ischemia/reperfusion (IIR)‐induced lung injury. Studies showed that administration of mast cell stabilizers both before ischemia and at reperfusion can dramatically attenuate IIR injury. However, the relative effectiveness of mast cell inhibition before ischemia or during reperfusion on IIR‐induced lung injury has yet to be determined. Cromolyn Sodium (mast cell stabilizer, 25mg/kg i.v.) was administrated either for 15 min before inducing small intestinal ischemia in mice by occluding the superior mesenteric artery for 30 min, or for 15 min upon reperfusion. Small IIR resulted in significant intestinal injury manifested as increased Chiuˈs scores with concomitant lung injury evidenced as elevations in lung injury scores, lung wet/dry weight ratio and increases in lung tissue tryptase and mast cell protease 7 protein expressions in lung in 3 hours after reperfusion, accompanied with decreased survival rates at 3 day after reperfusion (all P<0.05, vs. Sham control). All these changes were significantly alleviated in mice treated with Cromolyn Sodium on reperfusion (P<0.05, vs. IIR untreated) but not in mice pre‐treated with Cromolyn Sodium. The results indicate mast cell inhibition at early reperfusion is an effective therapeutic approach in attenuating intestinal IR mediated remote organ injury.

Supported by NSFC grant (30901408)
Localization and ERK signaling of α1‐adrenergic subtypes in human and mouse smooth muscle cells
Authors: Wright Casey D , Schwegel Jenica S , Anderson-Daniels Jordan M
Published: June 2021

Classic G‐protein coupled receptor (GPCR) mechanisms involve intracellular signaling initiated at the cell membrane leading to changes in cell function. However, recent evidence suggests GPCR localize to and signal from both the cell membrane and the nuclear membrane. Several cell types, including neurons, hepatocytes, and cardiac myocytes have functional GPCR at the nucleus. In cardiac myocytes, activation of nuclear alpha1 adrenergic receptors (α1‐AR) can protect cardiac myocytes from several cell death signals. Here we examined the localization and signaling of α1‐AR subtypes A, B and D in human vascular smooth muscle cells (SMC) and mouse prostate SMC. GFP fusion proteins of each α1‐AR subtype were infected into cultured SMC and visualized using confocal microscopy. In human vascular SMC and mouse prostate SMC, the α1A‐AR localized to the plasma membrane with some intracellular localization, whereas the α1B‐ and α1D‐AR localized mostly intracellularly. Activation of α1‐AR in human vascular or mouse prostate SMC lead to phosphorylation of ERK, however this response was only detectable following 48 hr of serum deprivation in culture media. Further experiments to determine the contribution of intracellular α1‐AR versus cell membrane α1‐AR to signaling could have an impact on treatments for hypertension and benign prostate hyperplasia. This work was supported by a grant from NIH (CDW).
Neuritogenesis initiated via the GPCR PAC1 requires cAMP and ERK signaling organized in a single linear pathway independent of PKA or Epac
Authors: Eiden Lee E. , Emery Andrew C.
Published: June 2021

Both cAMP and ERK are necessary for neuroendocrine cell neuritogenesis initiated through the PAC1 receptor, a family B GPCR activated by the neuropeptide PACAP (Ravni et al., Mol Pharmacology, 73:1688–16708). However, it is not yet known whether cAMP and ERK are arranged in two parallel pathways employing known signaling mechanisms, or a novel, linear pathway. We have measured cAMP elevation, ERK phosphorylation, CREB phosphorylation, neuritogenesis and cAMP/PKA‐dependent promoter‐reporter gene activation after treatment with forskolin, cAMP analogs, and PACAP in Neuroscreen‐1 (NS‐1) cells, a PC12 variant enabling simultaneous morphological, molecular biological, and biochemical analysis. Forskolin (25 μM) and cAMP analogs (8‐Br‐cAMP, db‐cAMP, 8‐ CPT‐cAMP) stimulated ERK phosphorylation and neuritogenesis in NS‐1 cells. Both ERK phosphorylation and neuritogenesis were MEK‐dependent (blocked by 10 μM U0126) and PKA‐independent (insensitive to 30 μM H‐89 or 100 nM PKI). CREB phosphorylation induced by PACAP was blocked by H‐89. The Epac‐selective 8‐pCPT‐2′‐O‐Me‐cAMP (100–500 μM) activated Rap1 without affecting the other cAMP‐dependent processes. Thus, PACAP‐38 potently stimulated two distinct and independent cAMP pathways leading to CREB or ERK activation in NS‐1 cells. We have thus identified a PKA‐ and Epac‐independent signaling pathway leading from cAMP elevation to ERK activation and thence neuritogenesis, that involves a novel cAMP sensor whose effects are insulated from those mediated by cAMP through PKA and Epac.

Supported by NIMH‐IRP project ZO1‐MH002386.
Mechanism of Antiapoptotic Action of P2Y6 Receptor in Mouse Pancreatic Beta Cells
Authors: Balasubramanian Ramachandran , Jayasekara M.P. Suresh , Jacobson Kenneth A
Published: June 2021

Though human pancreatic β‐cells are known to regenerate throughout adult life, type 1 and type 2 diabetic patients have a significant deficit in β‐cell mass through immune reactions and/or β‐cell apoptosis due to hyperglycemia. Therefore, new antidiabetic drugs to promote β‐cell survival as well as function are studied. P2Y6 receptors (P2Y6Rs) are a class of G‐protein coupled nucleotide receptors that activate the phospholipase‐C signaling pathway. Earlier reports indicated that P2Y6R stimulation promotes survival of smooth muscle cells, astrocyotma cells and mouse pancreatic β‐cells against cytokine‐induced apoptosis. Here, we explore the mechanism of mouse β‐cell survival and protection by P2Y6R activation during apoptosis. P2Y6R agonist P1‐(uridine 5′‐)‐P4‐( N4‐methoxycytidine 5′‐)triphosphate (MRS2957) significantly increased phosphorylation of MAP kinase in MIN6 cells when compared to untreated control cells. Also, changes in the expression of anti‐apoptotic proteins Bcl‐2 and Bcl‐xL were evaluated using Western blots. The cytoprotective efficacy of P2Y6R agonist against hydrogen peroxide‐induced apoptosis in MIN6 cells was analyzed using annexin V staining and caspase‐3 activity. The role of MAPK in P2Y6R action was investigated using a MAPK‐inhibitor in cells exposed to H2O2. Insight into the mechanism of antiapoptotic action mediated by P2Y6Rs in pancreatic β‐cells will be discussed.
Effects of inhaled popcorn butter flavorings diacetyl, acetoin and acetic acid alone and in combination on airway reactivity to methacholine in rats
Authors: Fedan Jeffrey S , Thompson Janet A , Zaccone Eric J , Goldsmith W Travis , Jackson Mark , Frazer David G , Hubbs Ann F
Published: June 2021

Inhalation of microwave popcorn butter flavoring induces clinical bronchiolitis obliterans in workers (“popcorn workers’ lung”). Diacetyl (D), a major component of many butter flavorings, is suspected as the primary etiologic agent. In rats, D inhalation caused marked damage in the respiratory epithelium. Acetoin (A) and acetic acid (AA) are also constituents of butter flavoring vapors and could contribute to toxicity of the mixture. Lung resistance (RL), dynamic compliance (Cdyn) and reactivity to methacholine (MCh) in terms of changes in RL and Cdyn, were measured in anesthetized rats 18 h after inhalation exposure to D, A and AA alone and in combination (D+A+AA). D (250 ppm) decreased basal RL and reactivity to MCh (RL); A (150 ppm) had no effect on basal values or reactivity to MCh; and AA (27 ppm) increased reactivity to MCh (RL). The mixed exposure (D+A+AA) increased basal Cdyn, decreased reactivity to MCh (RL), and increased the Cdyn response to MCh. Inhalation of lower flavoring concentrations [D (167 ppm) + A (118 ppm) + AA (18 ppm)], did not affect basal RL and Cdyn, but Cdyn responses to MCh were increased. The results indicate that A and AA neither mitigate or exacerbate D's effect on reactivity (RL), but inhalation of D+A+AA leads to more compliant lungs (Cdyn).
An anatomical study of mandibular bone: measurements and surgical relevance of mandibular and mental foramina in human skulls
Authors: Jin Chelsea , Fealey David , Pruski April , Erkuran-Yilmaz Cigdem
Published: June 2021

The mandible is prone to fractures caused by a wide variety of trauma, and is commonly fractured at the body, condyle, angle, and symphysis respectively. Mandibular fractures pose a great health risk due to the high possibility of injury to the mental neurovascular and inferior alveolar neurovascular bundles as they pass through their associated canals in the mandible. Since the location of mandibular and mental foramina and related structures are critical for the assessment of injury, our objective was to provide morphometric measurements of the mandibular structures. Thus, in 34 mandibular bones, on left (L) and right (R) sides, we measured the distances in millimeters between mandibular foramen and condyle (L: 37.59±0.62, R: 37.19± 0.6), mandibular foramen and angle (L: 21.97 ±0.66, R: 22.91±0.78), mental foramen to mental protuberance (L: 25.88±0.37, R: 26.22±) mental foramen to angle (L: 55.09±0.69 R: 53.08± 0.80) mental foramen to lower jawline (L: 12.19±0.27, R: 12.42±0.31) mental foremen and alveoli (L: 12.87±0.38 R: 13.20±0.43), circumference of the head of condyle (L: 46.26±0.74 R: 45.89±0.86), circumference of neck of condyle (L: 31.91±0.56 R: 32.46±0.65), thickness of angle of mandible (L: 5.19±0.20 R: 5.21±0.14) and thickness of mental protuberance (12.92±0.24).This study provides morphometric measurements for the surgery of the mandible and related structures.
Intratracheal instillation of TiO2 increases carotid‐femoral pulse wave velocity by suppression of eNOS and increasing IL‐6 in artery in rat
Authors: Wang Jiun-Jr , Wang Chin-Hao
Published: June 2021

Background

In addition to the damages to the lungs, inhaled nanoparticles may induce systemic proinflammatory and prothrombotic effects; however, its impacts to the alternation of arterial wall property have not been investigated.

Methods

Studies were performed on 32 male Sprague‐Dawley rats in 4 groups, in terms of different interventions [intratracheal instillation of titian dioxide (TiO2; D=20 nm; 4 mg/kg) or vehicle] and treatments [N‐acetylcysteine (NAC; 20 mg/kg; i.v.) or Xigris (10 mg/kg; i.v.); 5 min prior to TiO2 instillation]. The LV function and the carotid‐femoral pulse wave velocity (CFPWV) were assessed by the LV pressure‐volume and two intravascular pressure transducers, respectively. Blood were samples at baseline, 1, 3 and 5 hrs after TiO2 to assess serum creatine phosphokinase (CPK) and creatine kinase‐MB (CK‐MB). Nitric oxide (NO), methylguanidiene (MG), malondialdehyde (MDA) and C‐reactive protein (CRP) were examined at 5 hrs. The expressions of IL‐6 and eNOS in the thoracic aorta were examined.

Results

TiO2 instillation induced severe systemic thrombotic effects, increasing CFPWV by 50% (8.8±3.6 m/s vs. 13.7±4.0 m/s). Xigris pretreatment attenuated thrombotic effects with minor changes in biomarkers and CFPWV (12.9±4.1 m/s). NAC pretreatment attenuated the increase in CFPWV (10.1±2.6 m/s; P<0.05) along with reduced serum MG, MDA and CRP and tissue IL‐6 and increased eNOS, while thrombotic effects persisted.

Conclusion

Intratracheal instillation of TiO2 induced transit increase in arterial stiffness is associated with systemic inflammatory responses.
Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature
Authors: Haddock Rebecca Ellen , Hill Caryl Elizabeth
Published: June 2021

Diet‐induced obesity is associated with enhanced sympathetic outflow, as measured by release of noradrenaline. However, sympathetic nerves release other transmitters; ATP being especially important in control of vascular tone. Here we examined the purinergic and adrenergic components to nerve‐mediated vasoconstriction in small mesenteric arteries of Sprague‐Dawley rats fed a normal or high fat diet. Arteries were isolated, pressurised and smooth muscle membrane potential and vessel diameter measured in response to perivascular nerve stimulation. Innervation density was examined by histochemistry. Obesity increased the amplitude of nerve‐mediated vasoconstriction (P<0.05; 1–10Hz). At 1 and 5Hz, purinergic and adrenergic responses were augmented, while only the purinergic component was increased at 10Hz (P<0.05). Vasoconstriction at 1Hz in obesity was associated with larger purinergic excitatory junction potentials (P<0.05), exhibiting decreased rise time and rate of decay (P<0.05), without change in resting membrane potential. Spontaneous EJPs were also significantly increased in amplitude and frequency, as was the density of the sympathetic nerve plexus (P <0.05). We demonstrate that sympathetic nerve‐mediated vasoconstriction is enhanced by obesity due to upregulation of purinergic, in addition to adrenergic, neurotransmission. The study was supported by the NHMRC to REH (466009).
Assessment of cardiac function in mice using ventricular catheterization and MRI derived Pressure‐Volume loops
Authors: Wansapura Arshani , Dunn Scott , Giaquinto Randy , Wansapura Janaka
Published: June 2021

Stroke work normalized to end diastolic volume derived from pressure‐ volume (PV) relationships is regarded as a gold standard for measurement of the contractile status. Though conductance catheters are widely used to obtain PV relationships in the heart, it does not provide accurate measurements of absolute ventricular volumes. Magnetic resonance imaging (MRI) on the other hand provides accurate measurement of Left ventricular (LV) cavity volume but does not provide absolute measurement of LV pressure. The aim of this study was to demonstrate the feasibility of obtaining MRI volume data while invasively measuring LV pressure in wild type C57BL/6 and δ sarcoglycan null (Scgd−/−). LV pressure was measured invasively using a MR compatible fluid filled pressure transducer and volume data collected simultaneously from a 7 Tesla scanner at rest and during infusion of Dobutamine. Stroke work was calculated from the integrated area within the PV loop. Stroke work of Scgd−/− decreased from 2.8±0.56 mmHg mL at rest to 1.1±0.49 mmHg mL at stress but did not change significantly in WT. Decreased stroke work in Scgd−/− mice under stress was associated with LV pressure decline which may be related to vascular abnormalities in these mice as previously reported. This study demonstrates for the first time that invasive pressure and MRI derived volume measurements can be made simultaneously in mice.
Inhibition of Rho‐kinase decreases fetoplacental perfusion pressure under both normoxic and hypoxic conditions
Authors: Vajnerova Olga , Kafka Petr , Herget Jan , Hampl Vaclav
Published: June 2021

Acute hypoxia causes hypoxic fetoplacental vasoconstriction (HFPV). Rho‐kinase inhibits myosin phosphatase activity and therby modulates intracellular Ca2+ sensitivity of vascular smooth muscle and augments vasoconstriction. We tested whether inhibition of Rho‐kinase pathway in fetoplacental vessels inhibits HFPV. Isolated rat placenta was dually perfused (from both the maternal and fetal side) with physiologic salt solution saturated with normoxic gas mixture in constant flow rate. Rho‐kinase pathway was inhibited by Fasudil (10 μM) which caused significant decrease of fetoplacental perfusion pressure (from 38 ± 3 mmHg to 31 ± 3 mmHg, P < 0,01). Vasoconstriction induced by the acute hypoxic challenge was blocked. We measured fetoplacental perfusion pressure and fetoplacental vascular resistance as a relationship of vascular perfusion pressure to continually rising flow rate (P/Q). In acute hypoxia the slope of the P/Q relation was higher in the control group than in the group with Fasudil. The pressure axis intercepts with P/Q line did not differ. In summary, Rho‐kinase inhibition causes complete abolition of HFPV.

Supported by GACR 305/08/0108 and 2nd Faculty of Medicine, Charles University
X‐ray fluorescence microscopy of cortical brain structures across scales
Authors: Lam Ann , Ohayon Elan Liss
Published: June 2021

Although it is well recognized that endogenous metals play an important role in healthy brain function, relatively little is known about their precise colocalization with respect to their neurochemical counterparts and anatomical localization across scales. We used synchrotron‐based x‐ray fluorescence microscopy to explore this issue by imaging postmortem tissue from human cortical brain structures at multiple resolutions. Cortical tissue sampled from prefrontal, temporal and occipital postmortem brain structures were imaged at two beamlines at the Stanford Synchrotron Radiation Lightsource. Quantitative distributions of several metals were collected at resolutions ranging from 0.5 to 100 microns. Elemental maps of unstained tissue showed the differential distribution of metals such as zinc, iron, copper and calcium in gross brain structures as well as at the sub‐cellular level. The distribution of particular elements also varied across cortical tissue depth. We also illustrate the differential effects of various histological stains applied prior to x‐ray fluorescence imaging. The findings demonstrate the sensitivity of x‐ray fluorescence imaging and potential to be cross‐correlated with other neurochemical markers at scales ranging from the sub‐cellular to whole brain.

Support: NIH
Effects of spaceflight on vasoconstrictor and mechanical properties of mouse cerebral arteries
Authors: Hanna Mina , Stabley John N , McCullough Danielle J , Dominguez James M , Muller-Delp Judy M , Behnke Bradley J , Taylor Curtis R , Delp Michael D
Published: June 2021

There is evidence to indicate that cerebral blood flow is diminished in astronauts upon return to Earth. Further, data from ground‐based animal models simulating the effects of microgravity have shown enhanced vasoconstriction and stiffness of cerebral arteries. The purpose of this study was to determine the effects of 13 d spaceflight (STS‐135 shuttle mission) on myogenic vasoconstrictor and mechanical properties of mouse cerebral arteries. Basilar and posterior communicating arteries (PCoA) were harvested and prepared for in vitro experimentation. Myogenic vasoconstrictor responses were lower and vascular distensibility was greater in the basilar arteries of spaceflown mice (n=7) relative to ground control animals (n=12). The elastic properties of the PCoA, as characterized via nanoindentation, demonstrated a 37% reduction in stiffness from spaceflown mice relative to controls. These results demonstrate that spaceflight alters vasoconstrictor and mechanical properties of cerebral arteries and these changes may provide critical insight into the underlying cause of vision impairment in astronauts.

Supported by NASA grant NNX09AP06G