bluuebunny/crossref_metadata_2025 huggingface dataset:
Body Composition and Muscle Mass in Patients with Non‐Alcoholic Fatty Liver Disease: A Radiological Study Computed Tomography Analysis of Body Composition in Patients with Non‐Alcoholic Fatty Liver Disease
Authors: Foje Nathan , Khandalavala Birgit , Oliveto Jennifer , Rochling Fedja , Geske Jennene
Published: November 2023

Non‐alcoholic fatty liver disease (NAFLD) is rapidly becoming a leading cause of liver disease in the US, and it is predicted to become the predominant cause of liver failure and transplant in the future. There is a critical void in current knowledge of non‐invasive NAFLD evaluation and assessment and limited therapeutic options. Emerging data suggests that NAFLD is significantly correlated with metabolic abnormalities, insulin resistance, and visceral adiposity. Sarcopenia is increasingly reported to be associated with poor prognosis with similar correlations to metabolic status. Preliminary studies indicate that muscle mass can be reliably estimated on radiological evaluation by CT scan and is a good indicator of prognosis. With sparse data available on body composition that includes muscle mass estimation in patients with NAFLD in the US, a study to provide more comprehensive assessment, could lead to development of a novel muscle biomarker.

A retrospective cohort study was conducted for a mid‐western population with known NAFLD at a single institution. Following exclusion of other causes, 192 subjects with NAFLD were identified by chart review to have undergone incidental, abdominal, non‐contrast CT scans over a three‐year period. Specialized software was used to estimate body composition consisting of visceral adipose tissue and subcutaneous adipose tissue. Muscle mass was determined by psoas muscle measurement to provide the computed tomography abbreviated assessment of sarcopenia in trauma (CAAST) score as an indicator of sarcopenia.

This study demonstrated a reliable, low‐risk, and readily available methodology for comprehensive body composition in patients with NAFLD. The use of such non‐invasive and prognostic information could be essential for targeted interventions that would reduce the visceral adipose tissue, increase lean muscle mass, and improve outcomes.

Support or Funding Information

No dislosures
Effects of Probiotic Metabolites on iPSC Proliferation, Differentiation and Maturation
Authors: Wu Danielle , Fu Richard , Scoffield Jessica , Kannappan Ramaswamy
Published: November 2023

Recent studies discovered that bacteria can maintain and benefit human health. Probiotics, the live and benign bacteria, in yogurt could modulate the bacterial profiles in human gut, and thus have health benefits. We examined five different brands of yogurts often sold in the supermarkets (Oikos, Stonyfield, Yoplait, Chobani and Activia) by Gram‐staining bacteria, culturing bacteria, and identifying certain bacteria by PCR and DNA sequencing with bacterial fingerprinting 16s rRNA gene. We found that not all yogurts are produced equally, and some yogurts, such as Chobani Yogurt, contain more viable bacteria and they lived longer than bacteria from other brands. Sequencing analysis identified the presence of different probiotic bacterial strains in different yogurts. To evaluate the probiotic health benefits, we determined the effects of probiotic metabolites on human cardiac fibroblast derived induced pluripotent stem cells (iPSC). Using conditioned media from probiotic bacteria Lactobacillus reuteri (LRCM), we found that bacterial metabolites induced iPSC proliferation at lower doses while inhibited iPSC proliferation at higher doses. Additionally, the proliferating cell nuclear antigen PCNA was up‐regulated in iPSCs treated with LRCM and more interestingly, LRCM treatment potentiated the expression of pluripotent stem cell factors OCT4, SOX2 and NANOG in iPSCs. Consistently, a defined bacterial metabolite‐short chain fatty acid, sodium butyrate, had similar effect on iPSC proliferation. Furthermore, LRCM and butyrate exhibited similar effects on the differentiation of iPSC into cardiomyocytes, as indicated by myocyte beating and analysis of myocyte transcript markers. The results of cardiac myocyte differentiation and maturation will be discussed at the meeting as the experiments are ongoing. In summary, we have determined that probiotics in different brands of yogurts are different in viability and stains. Using conditioned media from a probiotic bacteria and a defined bacterial metabolite, we have further demonstrated the direct effects of probiotic metabolites on iPSC proliferation, differentiation and maturation. These studies have established a good platform to further study how the yogurt changes human microbiome and affects human health and disease.
The Protective Effects of Korean Ginseng Extracts on the Environmental Heat Stress in Sprague Dawley Rats
Authors: Choi Seo‐Yun , Song Ji‐Hyeon , Chei Sungwoo , Koh Eun‐Jeong , Choi Jia , Seo Young‐Jin , Park Min‐Ki , Hwang Ji‐Hyun , Lee Yeon‐Joo , Yang Byung Wook , Park Jong Dae , Lee Boo‐Yong
Published: November 2023

Increases in global average temperature cause a heat‐stress‐induced disorders by destroying the homeostasis. Therefore, excessive environmental heat stress disrupt the balance of immune system. Thus, protection of environmental heat stress is important for the regulation of immune homeostasis. Korean ginseng has been used for herbal medicine and has been known the beneficial biological properties. We determined that the Korean ginseng extracts (KGE) had the protective effects on heat stress by using analysis of heat‐stress‐induced rat model. As a results, heat stress dramatically increased water consumption and decreased food intake and body weight. However, KGE treated group was significantly reduced in the heat stress response. We also analyzed the blood contents such as serum cytokine, hormone, immunoglobulin (Ig) family and blood cells. Our results showed excessive heat exposure increased secretion of stress‐related hormone such as adrenocorticotropic hormone (ACTH) and cortisol whereas it was significantly reduced stress‐related hormone release on the KGE groups. Therefore, secretion of cytokine were changed in heat stress group. Particularly, Tumor necrosis factor‐alpha (TNF‐α) and Interleukin 2 (IL‐2) were significantly increased in .heat stress group compare with KGE treated groups. The production of Ig family were also showed similar tendency with secretion of cytokine. As a results, we expected that KGE has a protective effects against environmental heat stress by enhancing the immune homeostasis.
The inhibitory effect of Gomisin N on lipid accumulation during adipocyte differentiation
Authors: Choi Seo‐Yun , Lee Yeon‐Joo , Hwang Ji‐Hyun , Choi Jia , Koh Eun‐Jeong , Song Ji‐Hyeon , Seo Young‐Jin , Chei Sungwoo , Park Min‐Ki , Lee Boo‐Yong
Published: November 2023

Obesity is an energy balance disorder. It causes cardiovascular diseases, diabetes mellitus type 2 and certain types of cancer. These relationships rely on the excessive differentiation and proliferation of adipocytes, which leads to increased size and number of fat cells. It caused by over expression of lipogenic enzyme or surplus energy accumulation stored as TG in adipocytes. Inhibition of the adipogenesis and lipid accumulation in 3T3‐L1 adipocytes contributes crucial therapeutic effect on prevention of obesity.

In this study, we focused on anti‐obesity effect of Gomisin N (GN) in 3T3‐L1 adipocytes during differentiation. Accumulated lipid droplets were examined by Oil red O staining (ORO). The expression of adipogenic transcriptional gene were subjected by qPCR and Western Blot. The cells were incubated in the presence or absence of GN during differentiation. ORO showed that lipid accumulation was inhibited by GN in dose‐dependent manner. Moreover, the expression of adipogenic and lipogenic factors were suppressed by GN. Our data suggests that GN has an inhibitory effect of lipid accumulation in 3T3‐L1 cells.
Evaluation of anti‐obesity activity of different extracts from Grifola frondosa in vitro
Authors: Lin Pei‐Shan , Huang Chin‐Shiu , Huang Pei‐Jane , Han Chien‐Kuo , Chen Hsiao‐Ling
Published: November 2023

Grifola frondosa have been reported to have hypolipidaemic effects and several health benefits. However, the anti‐obesity activity and the optimal extract underlying these actions of G. frondosa have not been reported. In this study, we screened seven different extracts from G. frondosa to test their anti‐obesity activity using porcine pancreatic lipase assay in vitro activity. We also investigated the inhibitory effects of G. frondosa extracts on lipid droplet accumulation and cell growth during 3T3‐L1 preadipocyte differentiation. The lipase inhibitory activities of these seven extracts of G. frondosa were higher in the 50% ethanol extract than in other extracts. The 50% ethanol extract from G. frondosa also had highest inhibitory activity on cell growth and lipid accumulation during 3T3‐L1 cell differentiation. These results suggest that 50% ethanol extract of G. frondosa may have potential benefits as a health agent with anti‐obesity properties.

Support or Funding Information

This study was supported by a grant (MOST‐105‐2632‐B‐468‐001) from the Ministry of Education, Republic of China (Taiwan).
Tongqiaozuoxue Decoction, a Traditional Korean Medicine, Improves Hypercoagulation Through Stimulating Adiponectin Expression
Authors: Kim Soon‐Hee , Park Hee‐Sook , Hong MoonJu , Lee Ju Ah , Kim Myung‐Sunny
Published: November 2023

The efficacy and safety of traditional medicine could be proved through human trial for a long time, and now it has been required for the scientific evidence of its efficacy and identification of specific functional target. Tongqiaozuoxue Decoction (THD) is a water extract of 8 species of medicinal herb including Cnidium officinale Makino and Prunus persica Batsch, and has been used for the treatment of blood stasis and hypercoagulation in traditional Korean medicine. This study investigated the efficacy of THD and its functional target using animal model. Early vascular model was established through feeding high‐fat diet (HFD, 60% fat) for 12 weeks to C57BL/6 mice; these mice showed the phenotype of obesity, insulin resistance, chronic metabolic inflammation, hyperlipidemia, and prothrombotic state. THD was orally administered for last 4 weeks in a dose of 100mg/kg/day. THD significantly decreased plasminogen activator inhibitor‐1 (PAI‐1) level in serum and adipose tissue (AT) by 30% and 60%, respectively. Also, the plasma activity of tissue‐type plasminogen activator (tPA), the downstream target of PAI‐1, was increased by 2‐fold. Fibrin deposition was notably reduced in AT, demonstrated by immunohistochemistry. Meanwhile, adiponectin level was significantly increased both in serum and adipose tissue by 30% and 60%, respectively, although adipose tissue weight or total body weight were not changed by THD. Taken together, these results demonstrated that THD improve hypercoagulation through stimulating adiponectin expression.

Support or Funding Information

This study was supported by the grant of Korea Institute of Oriental Medicine
Peucedanum japonicum extract attenuates allergic airway inflammation by inhibiting Th2 cell activation and inflammatory mediators
Authors: Mi Chun Jin , Lee A‐Reum , Kim Hyo Seon , Lee A Yeong , Gu Gyo Jeong , Kwon Bo‐In
Published: November 2023

Background

Peucedanum japonicum Thunb is traditionally used to treat coughs, colds, headaches and inflammatory diseases in Korea and Japan. However, the effects of Peucedanum japonicum on allergic lung inflammation have not been investigated. The aim of this study was to investigate the anti‐asthmatic effects of Peucedanum japonicum extract (PJE) in ovalbumin (OVA)‐induced asthmatic C57BL6 mice and lipopolysaccharide (LPS)‐stimulated RAW264.7 cells. First, we evaluated the effects of PJE on airway inflammation in OVA‐induced asthmatic mice. Next, we investigated whether PJE inhibited the activation of Th2 cells both in vivo and in vitro, and identified inflammation related proteins in LPS‐stimulated RAW 264.7 cells.

Materials and methods

OVA was used to sensitize and challenge the airway of the mice, and PJE was orally administrated. We evaluated cell numbers, production of Th2 cell‐related cytokines in bronchoalveolar lavage fluid, histopathological features, and the levels of GATA‐binding protein‐3 (GATA‐3) in the lung. In addition, Th2 cell activation both in the lung and among primary cultured splenocytes was evaluated by Fluorescence‐activated cell sorting (FACS) analysis. Levels of inflammatory mediators and cytokines were determined in LPS‐stimulated RAW264.7 cells.

Results

PJE inhibited the OVA‐induced asthmatic response by reducing airway inflammation, and levels of Th2 cell related cytokines (IL‐5 and IL‐13). PJE inhibited the activation of Th2 cells both in vivo and in vitro via inactivation of CD4+ T cells, blockade of GATA‐3 expression, and reduction of the frequency of IL‐13‐producing cells after stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. Furthermore, PJE down regulated inflammatory mediators (iNOS and COX‐2) and proinflammatory cytokines (TNF‐α, and IL‐6) in RAW264.7 cells.

Conclusions

These results demonstrated that PJE inhibited the OVA‐induced asthmatic response by reducing airway inflammation. Consequently, PJE attenuates allergic airway inflammation by inhibiting Th2 cell activation and inflammatory mediators. These results indicate that Peucedanum japonicum is useful to treat allergic lung inflammation.

Support or Funding Information

This research was supported by grants for Evaluation of effectiveness of alternative herbal medicine resources (K14416 and K15411) from Korea Institute of Oriental Medicine (KIOM).
EVALUATION OF HAEMATOLOGICAL PROPERTIES OF WISTAR ALBINO RATS FED Curcuma longa (Turmeric) RHIZOME POWDER
Authors: Iwueke Adaku Vivien , Ihenacho Kizito , Nwodu Judith
Published: November 2023

The nutraceutical spice prepared from turmeric tubers used in many Asian cuisines possesses a diverse array of biological activities including anti‐inflammatory, anti‐neoplastic, and metabolic modifying properties among others. This study investigated the effect of intragastric administration of aqueous suspension of powdered Curcuma longa (turmeric) rhizome on haematological parameters of Wister albino rats. Twenty four male albino rats were randomly divided into four groups (A–D), receiving distilled water, 50, 100 and 200 mg/kg of the powder respectively for three weeks. The body weights of the animals were measured weekly, while haematological parameters were determined after three weeks. The result revealed that daily oral administration of graded doses of the C. longa powder for the study period showed a non‐significant increase in the body weights of the animals. Treatment with the powder did not significantly (P ≥ 0.05) alter the levels of hemoglobin (Hb), red blood cells (RBC) and means corpuscular volume (MCV) of the rats. The result also showed a significant (p ≤ 0.05) increase in the platelets and mean corpuscular hemoglobin concentrations (MCHC). However, the white blood cells (WBC) and the packed cell volume (PCV) concentrations were slightly reduced. These suggest that turmeric powder at the doses and duration used in the study has no adverse effect on haematological parameters.

Support or Funding Information

PERSONALY FUNDED
Antioxidant, antibacterial, cytotoxic activities of essential oil derived from Schisandra chinensis pulp and seeds
Authors: Chen Xiao‐qiang , Wang Huan , Zhang He , Zu Yuan‐gang , Chen C‐Y. Oliver , Zhang Ying
Published: November 2023

Plant derived essential oils (EO) possess antioxidant, antibacterial, antiviral, analgesic, anti‐inflammatory, and anti‐carcinogenic activity, making them a candidate ingredient for development of nutraceuticals, cosmetics, pharmaceuticals, and functional foods. Schisandra chinensis fruit (SCF) is one of the 50 fundamental herbs in traditional Chinese medicine, particularly used for indications relevant to blood sugar control, acid‐base balance, and uterus myotonic activity. In this study, we aimed to characterize chemical composition in EO of SCF pulps (PEO) and seeds (SEO), as well as to determine their antioxidant, antibacterial, and cytotoxic activities. SCF were collected in northern China. PEO and SEO were produced using a steam distillation method, and the respective yield was 0.18 and 1.72 %. Using GC‐MS, we identified 61 and 48 compounds in PEO and SEO, respectively, with p‐cymene (7.4%), 3‐methoxy‐p‐cymene (5.0%) and ylangene (4.7%) being the most abundant in the former and ylangene (23.1%), p‐cymene (6.0%) and α‐longipinene (5.9%) in the later. Further, most identified compounds are monoterpenes and sesquiterpenes and their oxygenated forms. Monoterpenes and sesquiterpenes comprise 30 and 45% of PEO, respectively, and 22 and 64% of SEO. Both PEO and SEO showed a very weak antioxidant activity against DPPH with the IC50 at 3.14 and 7.18 g/mL, respectively, as compared to BHT at 0.01 g/mL. Their TRAP and FRAP values were ≤0.03 mmol Trolox/g. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) towards Gram‐positive S. aureus and B. subtilis and Gram‐negative P. aeruginosa and E. coli were measured using an agar dilution method. Both PEO and SEO exhibited antibacterial activity against the four tested bacteria with the MIC ranging between 0.25 and 1.00 mg/mL and between 0.50 and 1.00 mg/mL, respectively, and the MBC ranging between 0.50 and 1.00 mg/mL and between 0.50 and 2.00 mg/mL, suggesting the constituents in PEO possess larger antibacterial efficacy. The cytotoxic effect of two EOs was evaluated in cultured human cervical HeLa, gastric BGC‐823, and lung A549 cancer cells. PEO and SEO diminished the viability of HeLa and BGC‐823 cells with IC50 ranging from 39 to 56 μg/mL, but was ineffective toward A549 cells. In conclusion, PEO and SEO are abundant in monoterpenes and sesquiterpenes and display modest antioxidant, antibacterial and cytotoxic activities with the former being better than the later.
Do Health Promoting Compounds of Flaxseed Attenuate Weight Gain via Regulation of Inflammation?
Authors: Mann Michael , Wiltgen Ashton , Silvernagel Kelsie , Rhee Yeong
Published: November 2023

Obesity increases pro‐inflammatory cytokine production leading to systemic inflammation. This study determined the effect of health promoting compounds of flaxseed on weight gain and inflammatory cytokine productions. Sixty C57BL/6J male mice were randomly assigned into one of the following diet groups and fed for eight weeks: 1) 45% Kcal fat; 2) 45% Kcal fat, 10% whole flaxseed; 3) 45% Kcal fat, 6% defatted flaxseed; 4) 45% Kcal fat, 4% flaxseed oil; and 5) 16% Kcal fat. Weight and dietary intake were measured weekly. Pro‐inflammatory cytokines, tumor necrosis factor (TNF)‐α and interleukin (IL)‐6, and nucleus factor (NF)‐κB expression in mouse liver samples were determined by real‐time quantitative PCR. The fold change in TNF‐α and IL‐6, and NF‐κB expression was calculated using 2‐ΔΔCT method. The average weight at pre‐treatment among diet groups was significantly different (p=0.013). The weight gain between pre and post diet treatments (p<0.0017) and the average weight at post‐treatment were significantly different (p<0.0001) among diet groups. Although there were no significant effects of diet treatment on selected gene expression, a positive correlation between TNF‐α and NF‐κB expressions (p<0.0001) and a positive trend between TNF‐α expression and weight gain (r=0.23324, p=0.075) were observed. The results indicated a possible mechanism of weight gain regulation by health promoting compounds of flaxseed via control of inflammation, which needs further study.

Support or Funding Information

NDSU HDE College and HNES Department
SHOULD ‘OMICS’ EDUCATION BE A PART OF ALLIED HEALTH PROFESSION CURRICULA?
Authors: Brown Hadley D , Boonme Kittipong , Imrhan Victorine , Juma Shanil D , Vijayagopal Parakat D , Prasad Chandan D
Published: November 2023

Our understanding of the role of nutrigenetics, nutrigenomics, epigenomics, and other ‘Omics’ in health and disease is increasing exponentially making personalized nutrition and lifestyle modification for better health a real possibility in the not too distant future. With this comes an urgent need of educating healthcare providers to enable them to have a meaningful conversation with healthcare consumers about ‘Omics Sciences’. The hurdles that lie in this path are ever shrinking physician time spent per patient and, more importantly, some physicians may even lack knowledge. Therefore, the burden of educating consumers may be on shoulders of allied health professionals such as dietitians, nurses, pharmacists, physician assistants, kinesiologists, occupational therapists, physical therapists and certified health educators. Towards this goal, the “International Society for Nutrigenetics & Nutrigenomics” would like to explore the possibility of advocating ‘Omics’ education to students in allied health professions. To support their advocacy, the society plans to collect data on the basic ‘Omics’ knowledge, attitude about ‘Omics’ education, and students' perception of need for such an education. Therefore, we plan to develop and validate a survey instrument to collect data of interest. The survey will include trainees from across the globe and a variety of allied health disciplines. Our initial survey will be limited to students in healthcare disciplines from Dallas‐Ft. Worth (Texas) area.
Impact of Training Primary Care Physicians in Behavioral Counseling to Reduce Cardiovascular Disease Risk Factors in Quito, Ecuador
Authors: Fornasini Marco , Baldeon Manuel Eduardo , Zevallos Juan Carlos , Flores Nancy , Rosal Milagros , Merriam Philip , Ockene Ira
Published: November 2023

Background

Previous published literature has shown that cardiovascular risk factor management programs conducted during physician visits in developed countries result in a decrease in the risk for cardiovascular diseases. The purpose of this study was to determine the feasibility of a physician‐training program for diabetes and cardiovascular risk reduction in an at‐risk population in Ecuador, a developing country now facing a rapidly increasing incidence of diabetes and cardiovascular disease.

Methods

A randomized clinical trial was conducted in 6 primary care clinics in Quito, Ecuador. Participants included 15 primary care physicians (PCPs) and a sample of their adult patients at risk for type‐2 diabetes. A twelve‐step physician‐based and patient‐centered counseling training program aimed at decreasing cardiovascular risk was delivered to 8 PCPs. Seven additional PCPs who did not receive the training comprised the control group. The patient experience regarding counseling steps addressed by their physician was assessed by patient exit interviews (PEIs) which were administered immediately following the first post‐recruitment patient appointment. Anthropometrics, blood pressure, blood biochemistry parameters, and assessment of patient compliance with medication were conducted at baseline and after 6‐months follow‐up. Changes from baseline as well as differences between groups were estimated utilizing Chi‐square, ANOVA and paired t‐tests.

Results

A total of 197 patients were enrolled, 113 in the intervention care (IC) group and 84 in the usual care (UC) group; 99 patients (87.6%) in the IC group and 63 (75%) in the UC group completed the study between June 2014 and June 2016. Overall, participants from both study groups had similar socio‐demographic characteristics. The mean number of completed counseling steps, as measured by the PEI, were significantly higher in the IC group (8.9±1.6 vs. 6.6±2.3; p=0.001) and a significant reduction in glycated hemoglobin was seen in that group; p=0.023. Data also showed that within the IC group there were significant improvements in weight, Body Mass Index, total cholesterol, and LDL‐cholesterol.

Conclusions

Our findings show that training PCPs in patient‐centered counseling for cardiovascular risk factor reduction is successful. Implementation of this educational strategy in Ecuador and other countries undergoing an epidemiologic transition could reduce both diabetes and cardiovascular risk among high‐risk patients.

Support or Funding Information

International Atherosclerosis Society& Pfizer International
Sex Differences in Placental Mitochondrial Function Associated with Ozone‐Induced Fetal Growth Restriction
Authors: Miller Colette N , Lavrich Katelyn S , Freeborn Danielle , Kodavanti Prasada R , Kodavanti Urmila , Dye Janice A
Published: November 2023

Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularly in terms of increased placental weight and mitochondrial DNA levels, have been demonstrated in intrauterine growth restricted (IUGR) fetuses. Little is known about the mechanisms that drive placental maladaptation that can contribute to compromised fetal development, thus we sought to explore them in our model of IUGR. In the current study we developed a model of IUGR by exposing Long Evans dams to filtered air or 0.8 ppm ozone, 4hr/day during the implantation period. At gestational day 21, pups from ozone exposed dams had reduced weight compared to air control pups, demonstrating the development of IUGR. Furthermore, placenta to pup weight was elevated in both male and female IUGR pups, suggesting impaired placental development. Bioenergetics, measured as oxygen consumption rate (OCR), on fresh placental mitochondria were measured using the Seahorse XF96 analyzer. While IUGR did not impact female placental OCR at any point in the assay, placentas of IUGR males had increased total OCR relative to controls. Total ATP production remained unchanged between control and IUGR male placentas, however a significant proton leak was found in the mitochondria from male IUGR placentas compared to controls. Despite apparent sex differences in placental mitochondrial OCR, both sexes of IUGR pups had elevated mitochondrial biogenesis and mitochondrial DNA levels compared to their respective controls. Additional gene expression experiments demonstrated that female IUGR pups have reduced Sod1 and increased Bcl2 expression compared to control female placentas, suggestive of increased apoptosis. Interestingly, this difference was not observed in males. Together our data supports the hypothesis that placental mitochondrial dysfunction is related to reduced fetal weight. However, we demonstrate clear sex differences of IUGR on mitochondrial function and activity in the placenta. Our findings support the emerging importance of mitochondrial health in the etiology of environmental stress‐induced IUGR, as well as the importance of utilizing a sex‐specific approach to investigate prenatal outcomes. This abstract does not reflect US EPA policy.

Support or Funding Information

This abstract was funded by the US EPA.
Exposure to Oxidized Tyrosine Products Induced Glycometabolism Disorder Involving Thyroid Hormones Resistance in C57BL/6 mice
Authors: Ding Yinyi , Li Zhuqing , Ran Yumei , Shi Yonghui , Le Guowei
Published: November 2023

Oxidative modifications of aromatic amino acids can be easily found in protein‐riched food, such as meat and milk products. Tyrosine is one of the most easily oxidized amino acids, leading to formation of dityrosine, 3‐nitrotyrosine, and 3‐chlorotyrosine. Although many researches has started to focus on the protein oxidation in meat and dairy products, the influence of dietary oxidized protein on metabolic disturbance has not been fully explored. Thyroid hormones (THs) are widely known for their ability to influence various cellular processes. Previous studies demonstrated that thyroid hormone resistance (RTH) is associated with impairment of glucose metabolism. This study was to determine whether oxidized tyrosine products (OTPs) exposure could inhibit the thyroid hormone action in pancreas leading to glucose metabolism disorder. We found that OTPs exposure (640 μg/kg bw/day, 10 weeks) induced increased blood glucose and decreased plasma insulin content in C57BL/6 mice. These data reflected glucose metabolism disorder in OTPs mice. OTPs induced elevated plasma free THs in the presence of unsuppressed thyroid stimulating hormone (TSH) level. OTPs also altered mRNA levels of HPT‐axis related genes in hypothalamus, pituitary, and thyroid gland and histopathological data of thyroid gland. These data reflected that OTPs induced the resistance of THs to the normal negative feedback mechanism in the hypothalamus and pituitary, which is the character of RTH. The downregulation of membrane transporter of THs (MCT8) and protein level of thyroid hormone receptor β1 (TRβ1) illustrated the decreased sensitivity to THs in pancreas. In addition, lower mRNA level of TRs co‐activator factors (RXRα, Src‐1) in pancreas suggested the activation ability of THs to downstream gene involved in insulin synthesis (MafA) was suppressed by OTPs. Taken together, these findings suggested that OTPs triggers glucose metabolism disorder via thyroid hormone resistance in pancreas. To the best of our knowledge, this study is the first time to demonstrate that OTPs exposure is a risk factor of RTH in pancreas and inhibits insulin secretion.

Support or Funding Information

This research was supported by program of “Collaborative innovation center of food safety and quality control in Jiangsu Province”, the National Natural Science Foundation of China (No. 31571841), State Key Laboratory of Food Science and Technology of Jiangnan University in China (SKLF‐ZZB‐201609).
Histopathological dissection of three different osteoporosis animal models including ovariectomy female, F VIII knockout and Akr1A1 knockout mice
Authors: Lin Wei‐Yu , Chang Ro‐Lin , Liu Yao‐Wen , Chen Chuan‐Mu
Published: November 2023

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength, predisposing individuals to an increased risk of fracture. In our previous studies, we established two different osteoporosis animal models including coagulation F VIII knockout mice (genetic defect model) and Akr1A1 knockout mice (nutritional imbalanced model). We found that the degrees of bone loss in these two models are different from traditional ovariectomy (OVX) model, therefore we use micro‐computed tomography (μ‐CT) to analysis bone microarchitecture changes in these three different osteoporosis models. Six groups were designed for bone histopathological analyses in this study, including male and female B6 mice, OVX B6 mice, male ICR mice, male F VIII knockout mice and male Akr1A1 knock‐out mice. In the analysis of femurs trabecular bone parameters, bone volume/tissue volume (BV/TV) and trabecular separation (Tb.Sp) were most serious loss in OVX group; whereas trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular bone mineral density (Tb.BMD) were most serious loss in F VIII knockout group. It is worth mentioning that although Akr1A1 knockout mice exhibited bone loss compared with control (ICR) group, but not significantly loss than F VIII knockout mice and OVX mice. In the image of femurs cortical bone, bone morphology was obviously shorter in length enlarged in cavity in Akr1A1 knockout mice. In the blood biochemical parameters, carboxyl‐terminal cross‐linking telopeptides of type I collagen (CTX‐1) was highest in Akr1A1 knockout mice, alkaline phosphatase (ALP) and osteocalcin (OC) were significantly decreased in OVX group. Present data demonstrate that the animal models of OVX, F VIII knockout and Akr1A1 knock‐out can be used to represent different types of osteoporosis and to provide feasible platforms for the investigations of osteoporosis and drug development.
Incidence of Obesity among Employees in a Nigerian University
Authors: Emiloju Opeyemi C. , Chinedu Shalom N. , Iheagwam Franklyn N , Onuoha Micheal
Published: November 2023

Obesity has been on the increase worldwide and is presently recognized as one of the major health problem of our time. Obesity, usually exemplified by an increase in body fat at adipose tissue site, increases the risk of developing chronic diseases such as cardiovascular diseases, diabetes, and cancer. This study examined the prevalence of overweight and obesity among employees in a Nigerian University. A total of 727 subjects (280 females and 447 males), aged 20–78 with the age bracket 20–39, 40–59; ≥ 60 and above took part in this study. The weight and height of subjects were taken using standard measuring kit. The Body Mass Index (BMI) was calculated as weight per square of height (kg/m2) and WHO cut off was used to categorize the BMI of subjects into underweight, normal weight, overweight and obesity. The prevalence of underweight, normal weight, overweight and obesity among subjects include 1.65%, 35.49%, 31.50% and 31.36% respectively. Among the female subjects, the prevalence of underweight, normal weight, overweight and obesity was calculated to be 1.07%, 29.29%, 27.14% and 42.5% respectively while that of the male subjects was calculated to be 2.01%, 39.37%, 34.23% and 24.38% respectively. The study showed that over 60% of the subjects are overweight or obese. The incidence of obesity was observed to be higher among female subjects than among male subjects. The result of the study suggest a need for regular weight checks among employees in Nigeria in order to encourage necessary prevention strategies against obesity and its related diseases.
Pulsed‐Wave Doppler Blood Flow Through the Pulmonary Trunk as a Valuable Method to Determine Cardiac Output Following Myocardial Infarction
Authors: Platt Mathew J , Huber Jason S , Brunt Keith R , Simpson Jeremy A
Published: November 2023

Background

Cardiac output (CO) is a valuable measure of cardiac function, both clinically and in small animal models of cardiac injury (e.g., myocardial infarction; MI). As the product of stroke volume and heart rate, CO can be estimated from cardiac volumes acquired from one (i.e., M‐Mode) and two (i.e., single plane ellipsoid formula) dimensional echocardiographic images of the left ventricle (LV). Critically, deformations of the LV following MI (e.g., non‐uniform composition/contractile properties) invalidate the mathematical assumptions imperative to the accurate estimation of CO. Thus, the purpose of this study was to determine if pulsed‐wave Doppler flow through the pulmonary trunk – a structure independent of the remodeling in the ischemic LV – provided an alternative, and more accurate, method to quantify forward CO following MI.

Methods

Variations in CO were induced either by transverse aortic constriction (TAC) or MI. CO was calculated from classical LV‐dependent methods (M‐Mode and the single‐plane ellipsoid 2D formula), pulsed‐wave Doppler through the pulmonary trunk (pulmonary flow), and intra‐thoracic flow probe.

Results

In healthy mice, all three echocardiography methods (M‐Mode, 2D and pulmonary flow) correlated well with flow‐probe derived CO as confirmed by Bland‐Altman analysis. In MI, only pulmonary flow demonstrated both accuracy and precision, retaining the expected positive bias and demonstrating <10mls/min range difference compared to the 20–25mls/min range for either LV‐dependent method. Pulmonary flow CO in MI also demonstrated reduced inter‐ and intra‐user variability, and both an improved internal and external agreement (correlation coefficients) when compared against either M‐Mode or 2D CO calculations.

Conclusions

Pulmonary flow CO calculated from pulsed‐wave Doppler through the pulmonary trunk was an improved method of estimating CO over LV‐dependent formulae following MI. There was also a significant correlation between pulmonary flow, M‐Mode and 2D measures in healthy and TAC mice, demonstrating pulmonary flow was a comparable estimation of CO in these non‐ischemic conditions. This is relevant in the continuing attempt to more accurately assess cardiac function and particularly, grade preclinical therapies for treating MI.

Support or Funding Information

This work was supported by the Canadian Institutes of Health Research grant (MOP 111159) to J.A. Simpson. J.A. Simpson is a New Investigator of the Heart and Stroke Foundation of Canada.
The p53‐specific inhibitor pifithrin‐α prevents diabetic cardiomyopathy by attenuating the early‐stage apoptosis and improving late‐stage defects in glycolysis and angiogenesis
Authors: Gu Junlian , Cai Lu
Published: November 2023

Rational

Elevated expression levels of the tumor suppressor p53 have been associated with various heart diseases, including diabetic cardiomyopathy (DCM). However, its underlying mechanisms are unclear.

Object

Early cardiac cell apoptosis, the persistent reduction in glucose uptake and utilization, and an inadequate neovascularization may play important roles in the pathogenesis of DCM. The present study observed an upregulation of p53 in the heart of streptozotocin‐induced type 1 diabetes mice compared to nondiabetic mice. The aim of this study was to determine the protective mechanism and effect of pifithrin‐α in DCM.

Methods and Results

FVB mice were treated with five daily injections of 50 mg/kg streptozotocin to induce type 1 diabetes. Both hyperglycemic and age‐matched control mice were treated with or without pifithrin‐α five times a week for 2 months and then kept without treatment until 3 and 6 months. Treatment with pifithrin‐α significantly improved the progression of diabetes‐induced cardiac remodeling and dysfunction (i.e., DCM). Mechanistically, the inhibition of p53 prevented cardiac mitochondrial cell death during early‐stage diabetes (0.5 month) as well as prevented diabetes‐induced impairment of glucose metabolism and angiogenesis by increasing hypoxia‐induced factor (HIF)‐1α protein stability and upregulating the HIF‐1α transcription of specific protective genes at the later stages (3–6 months).

Conclusions

These results demonstrate for the first time that the inhibition of p53‐mediated early‐stage apoptosis and late‐stage defective glycolysis and angiogenesis effectively prevents the development of DCM, thereby suggesting that an intervention involving P53 may be a potential approach for the prevention of DCM.
Blood Plasma Concentration and Activity of Pancreatic Lipase, Pancreatic Trypsin, MMP‐9, and Elastase in Congestive Heart Failure
Authors: Courelli Vasiliki , Courelli Asimina , Stimson Ella , Modestino Augusta , Mills Paul , Schmid‐Schoenbein Geert
Published: November 2023

Recent evidence suggests that pancreatic digestive enzymes may be involved in several types of organ dysfunction. This may include heart disease, but no studies exist. We hypothesize that pancreatic trypsin, pancreatic lipase, MMP‐9, and elastase may be present in blood and cardiac muscle in patients with congestive heart failure (CHF). Pancreatic enzymes may leak out of the small intestinal lumen, enter the systemic circulation and, ultimately, cause damage of the heart muscle. Pancreatic proteases, such as trypsin, are capable of activating other proteases, such as MMP‐9. Blood was drawn from 20 patients (10 CHF and 10 non‐CHF patients) while at rest. Western Blots showed a significant increase in plasma pancreatic lipase, trypsin, and MMP‐9 levels for the CHF patients when compared to non‐CHF patients. Activity assay results showed a significant increase in plasma MMP‐2/9 activity levels in CHF compared to non‐CHF patients but no differences in trypsin and elastase activity. These pilot experiments suggest that elevated plasma trypsin, lipase, and MMP‐9 concentrations as well as plasma MMP2/9 activity are correlated with CHF, may play a role in the loss of cardiac function, and may serve as potential biomarkers for CHF.

Support or Funding Information

NIH Grants: 5 R01 HL073355‐01, GM 85072
Fibrinogen alpha is the precursor protein of cardiac valve amyloidosis
Authors: Miura Katsutoshi , Katoh Hideki , Tsuchida Takashi
Published: November 2023

Amyloid deposits are frequently found in degenerated cardiac valves of elderly patients. However, their precursor proteins have not detected to date. The aim of this study is to analyze the contents to reveal their original proteins.

Materials and Methods

Amyloid fibrils (AFs) were collected from fresh cardiac valves of aortic stenosis patients. AFs were separated by saline precipitation, collagenase or pepsin digestion and water extraction. AFs were dissolved in 6 M urea and isolated by SDS‐PAGE. Main bands in the gel were analyzed by MS spectrometry.

Several candidate proteins were picked up and their location on the histological sections were detected by immunohistochemistry. Fibronectins, fibrinogen alpha chains (FGA), vitronectins, lysozymes and complement 3 were stained whether they were co‐localized with amyloid.

Results

Only FGA were revealed to be present with amyloid deposits. FGA were scattered in the valves with random orientation and some areas showed co‐localization with amyloid deposits.

Conclusion

FGA is the precursor protein of localized cardiac valve amyloidosis.

Support or Funding Information

This work was supported by the Japan Society for the Promotion of Science KAKENHI, Scientific Research Grant Number (c) 15K08375.
Dipeptidyl Peptidase‐4 (DPP‐4) inhibition with linagliptin reduces the induction of proinflammatory/profibrotic TRAF3IP2 in the hearts of female mice fed a Western Diet
Authors: Aroor Annayya , Kandikattu Hemanthkumar , Habibi Javad , Garro Mona , Klein Thomas , Sowers James R , Valente Anthony J , DeMarco Vincent , Bysani Chandrasekar
Published: November 2023

Recently we reported that the cytoplasmic adapter molecule TRAF3 Interacting Protein 2 (TRAF3IP2) is a major mediator of myocardial inflammation, hypertrophy, fibrosis, and dysfunction induced by chronic activation of the renin‐angiotensin‐aldosterone system. Whether TRAF3IP2 and its downstream intermediates contribute to western diet (WD)‐induced myocardial fibrosis and dysfunction is not known. We have previously reported that the DPP‐4 inhibitor linagliptin prevents diastolic dysfunction and myocardial fibrosis in female mice fed a western diet (WD) high in fat and refined sugars. We hypothesized that WD induces myocardial overexpression of TRAF3IP2 and activation of downstream signaling intermediates, and their induction can be prevented by linagliptin. We fed 4‐week old mice a WD with or without linagliptin (83mg•kg−1diet) for 16 weeks, and evaluated diastolic function, cardiac TRAF3IP2 expression, transcription factor and p38 MAP kinase activation. WD feeding induced a two‐fold increase in TRAF3IP2 expression, with similar increases in the activation of pro‐inflammatory and pro‐fibrotic transcription factors p65 (Ser536) and c‐Jun (Ser63), and the stress‐activated kinase p38 MAPK (Thr180/Thy182). Importantly, linagliptin inhibited their activation. Our results demonstrate for the first time the induction of myocardial TRAF3IP2 protein expression and downstream proinflammatory/profibrotic signaling intermediates in a translationally relevant model of diet‐induced obesity. Therapeutic targeting of DPP‐4 with linagliptin or pharmacological inhibition of TRAF3IP2 may be a promising strategy for prevention of cardiac inflammation, dysfunction and fibrosis in females with obesity/diabetes.

Support or Funding Information

This work was supported by unrestricted funding from Boehringer Ingelheim (VGD). Additional support was provided by the National Institutes of Health [R01‐HL073101 RO1‐HL107910 to JRS], Veterans Affairs Merit System (I01‐BX002255 to BC and 0018 to JRS).
Histamine causes endothelial barrier disruption via Ca2+‐mediated RhoA activation and enhanced force generation at intercellular junctions
Authors: Rotkopf Lukas , Kugelmann Daniela , Walter Elias , Radeva Mariya , Waschke Jens
Published: November 2023

During inflammation, disruption of endothelial adherens junctions (AJ) and tight junctions (TJ) leads to increased microvascular permeability. In this study we used histamine to induce acute endothelial barrier breakdown in primary human microvascular endothelial cells. Using FURA‐2AM we observed a rapid Ca2+ influx induced by both histamine and thrombin accompanied by reduced transendothelial electric resistance (TER). Breakdown coincided with increased stress fiber and focal adhesion formation. The histamine response was blocked by the histamine receptor type 1 antagonist (H1R) diphenhydramine but not by the H2R antagonist ranitidine. Interestingly, GLISA measurements revealed activation of RhoA but not inactivation of Rac1 at the time‐point of barrier breakdown. FRET measurements showed activation of RhoA at intercellular junctions after both thrombin and histamine exposure. At the same time course we observed increased tension at AJs indicated by immunostaining with a conformation‐sensitive antibody targeting the α18‐subunit of α‐catenin. Both Ca2+ chelation by BAPTA‐AM and inhibition of ROCK1 abolished increased tension along AJs and barrier dysfunction in TER. Since BAPTA‐AM decreased RhoA activation following histamine stimulation, the data suggest a key role of Ca2+ signaling in barrier breakdown. Our data suggest that the patterns of signaling mechanisms engaged in acute inflammatory barrier disruption differ to more delayed responses as seen in sepsis. In response to histamine, Ca2+ via RhoA/ROCK activation leading to increased tension along junctions appears to be critical for barrier disruption.
Comparison between anti‐β2 Glycoprotein I antibody and anti‐phosphatidylserine/prothrombin antibody pro‐thrombotic effects on peripheral blood monocytes and endothelial cells
Authors: Cifu' Adriana , Fabris Martina , Pistis Cinzia , Domenis Rossana , Quaglia Sara , Curcio Francesco
Published: November 2023

BACKGROUND

Antiphospholipid Syndrome (APS) is a systemic autoimmune disease characterized by vascular thrombosis (venous or arterial) and/or adverse obstetric outcomes, accompanied by persistent and elevated levels of antiphospholipid (aPL) antibodies, namely lupus anticoagulant (LA), anticardiolipin (aCL) and anti‐β2 glycoprotein I (aβ2GpI) antibodies. However, there are several other aPL that are still not included in the diagnostic criteria, but that can be useful to better define the so‐called seronegative APS patients (negative for LA, aCL and aβ2GpI), such as anti‐phosphatidylserine/prothrombin (aPS/PT) antibodies. The aim of this study was to compare the pro‐thrombotic effects of aβ2GpI IgG and aPS/PT IgG antibodies on peripheral blood mononuclear cells (PBMC) and human umbilical vein endothelial cells (HUVEC) to support the independent role of aPS/PT in APS pathogenesis and diagnosis.

METHODS

PBMC isolated from blood donors (BD) and HUVEC (Life Technologies) were incubated four hours with lipopolysaccharides (LPS) alone or in combination with the IgG fraction obtained from a pool sera of BD (as control), and from a pool sera of 3 APS patients who were positive only for IgG aβ2GpI and from 3 APS patients who were positive only for IgG aPS/PT. TF mRNA up‐regulation, expressed as fold increase in respect to unstimulated cells, was measured by real‐time PCR. The experiments were done in triplicate.

RESULTS

Compared to treatment with LPS alone (6.4±1) or LPS plus the IgG fraction isolated from BD (6.5±1.7), PBMC stimulated either with LPS plus aβ2GpI IgG or with LPS plus aPS/PT IgG demonstrated an increased expression of TF (respectively 8.2±0.9 and 9.4±1.3; vs LPS + BD IgG p<0.05), but no difference was found between aβ2GpI and aPS/PT.

Similarly, the HUVEC stimulated with LPS plus aβ2GpI or aPS/PT displayed a significant increase of TF expression (respectively 90±7 and 87±2) compared to stimulation with LPS alone (18.4±5; p=0.04) or plus the IgG fraction from BD (9.45±2.9; p=0.01).

CONCLUSIONS

This is the first direct comparison between the aβ2GpI and aPS/PT pro‐thrombotic effects in vitro on monocytes and endothelial cells. Our data show that both aβ2GpI and aPS/PT antibodies were able to upregulate TF expression in monocytes and HUVEC pre‐activated with LPS. As expected, the effect was stronger in endothelial cells than in monocytes, but no difference was appreciated between aβ2GpI and aPS/PT. These results suggest that aPS/PT antibodies exert an independent role on APS‐related manifestations.