bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Lycium Barbarum Polysaccharides Extract and Betaine on Cell Activation and Liver Fibrosis in Rat Hepatic Stellate HSC‐T6 Cells
Authors: Chao Jane C‐J , Li Bo‐Ying 
Published: November 2023

The fibrogenesis is indicated by the activation of hepatic stellate cells (HSCs) and accompanied with enhanced secretion of transforming growth factor‐β (TGF‐β) and deposition of extracellular matrix. We determined the effects of Lycium barbarum polysaccharides (LBP) and betaine on cell activation and fibrotic markers after the activation of rat HSC‐T6 cells by H2O2. The results showed that H2O2 at 5 μM activated HSC‐T6 cells by significantly increasing the expression of alpha‐smooth muscle actin (α‐SMA), TGF‐β, and matrix metalloproteinase (MMP)‐2, which were significantly reduced by LBP and betaine at 10 and/or 50 μg/mL (p<0.05). The expression of tissue inhibitor of metalloproteinase‐1 (TIMP‐1) was significantly inhibited by LBP at 10 μg/mL, however, the expression of TIMP‐2 was promoted by betaine at 10 μg/mL. Therefore, LBP and betaine, the active components in Lycium barbarum L., attenuate liver fibrosis through inhibiting cell activation of HSCs and expression of fibrotic markers under H2O2‐induced oxidative stress.Support or Funding InformationThe study is supported by the Ministry of Science and Technology, Taiwan (grant no. 105‐2320‐B‐038‐036‐MY3).
Glutathione concentration and glutathione peroxidase activity are associated with the risk of liver cirrhosis independently of oxidative stress
Authors: Huang Yi‐Chia , Cheng Shao‐Bin , Liu Hsiao‐Tien , Lai Chia‐Yu 
Published: November 2023

Oxidative stress has been observed to be associated with the risk of liver cirrhosis. Glutathione is synthesized in the liver, with its dependent antioxidant enzymes play important roles in antioxidant defense system. However, the relationship between oxidative stress and the glutathione antioxidant system to mediate the risk of liver cirrhosis has not been clearly determined. We investigated whether the glutathione antioxidant system is dependent or independent of oxidative stress linked with the risks for liver cirrhosis. This was a case control study. Sixty‐eight patients with liver cirrhosis (case) and 110 healthy subjects (control) were recruited. Patients with liver cirrhosis had significantly lower glutathione concentrations and higher glutathione peroxidase (GPx) activity than healthy subjects. There was no significant difference in oxidative stress status between groups. Plasma glutathione is significantly correlated with GPx activity (r = −0.22, p < 0.05) and oxidative stress indicator (r = 0.31, p < 0.01) in all subjects. Subjects with higher plasma glutathione concentration exhibited significantly decreased risk of liver cirrhosis (odds ratio, 0.95; p = 0.01), while subjects with lower plasma GPx activity significantly increased the risk of liver cirrhosis (odds ratio, 1.03; p < 0.01) with adjustment for potential confounders. Glutathione and GPx activity plays a significant role in the risk of liver cirrhosis.Support or Funding InformationThis study was supported by the Ministry of Science and Technology, Taiwan (MOST 104‐2320‐B‐040‐009‐MY3).
In vitro anticancer efficacy of a polyphenol combination of curcumin, quercetin, green tea extract and resveratrol in human cervical cancer HeLa cells
Authors: Roomi M Waheed , Rath Matthias , Niedzwiecki Aleksandra 
Published: November 2023

Cervical cancer is the third most commonly diagnosed cancer and fourth leading cause of mortality in women worldwide. Although fully treatable in the early stages, once it has metastasized, the survival rate is 68%. Based on its poor prognosis, we investigated the effect of a specific polyphenol combination (PB) of curcumin, quercetin, green tea extract and resveratrol on viability, invasion, MMPs secretion and morphology on human cervical cancer HeLa cells. Cervix HeLa cells (ATCC) were cultured in DEM media, supplemented with bovine serum and antibiotics in 24‐well tissue plates. At near confluence, cells were treated with PB at 0, 10, 25, 50, 75 and 100 μg/ml concentration in triplicate at each dose. Cells were also treated with PMA for MMP‐9 induction. Cell proliferation was evaluated by MTT assay, MMPs by gelatinase zymography, invasion by Matrigel and morphology by H&E staining. PB inhibited proliferation by 10, 25, 30, 30 and 60% at 10, 25, 50, 75 and 100 μg/ml concentration. Zymography demonstrated expression of MMP‐2 and MMP‐9, with strong induction of MMP‐9 by PMA. Both MMPs were reduced by PB with total block at 50 μg/ml concentration. PB inhibited invasion through Matrigel at 25 μg/ml concentration. H&E staining showed no morphological changes up to 50 μg/ml concentration and exhibited apoptotic changes at 75 and 100 μg/ml concentrations. These results suggest that PB has promising new therapeutic potential in treatment of cervical cancer.Support or Funding InformationDr. Rath Research Foundation, a non‐profit organization
Effect of 4 weeks of high‐intensity interval training on exercise performance and markers of inflammation and oxidative stress
Authors: Zwetsloot Kevin A. , Nieman David C. , Knab Amy , John Casey S. , Lomiwes Dominic D. , Hurst Roger D. , Gillitt Nicolas D. , Lila Mary A. 
Published: November 2023

Prolonged, high intensity exercise induces substantial systemic inflammatory and oxidative stress responses. High intensity interval training (HIIT) involves bursts of heavy exertion separated by short rest periods; however, there is limited research on the effect of regular HIIT on the acute immune and oxidative stress responses to exercise. The purpose of this study was to determine the acute and chronic exercise‐related physiological responses and adaptation to 4‐weeks of cycling HIIT. We hypothesized that 4 weeks of HIIT would induce an attenuated inflammatory and oxidative stress response to an acute bout of HIIT. Sixty‐one sedentary, but healthy participants (males: n=15, 21.8 ± 1.0 y, initial VO2max = 37.7 ± 1.7 ml•kg−1•min−1, body fat = 16.8 ± 1.6%; females: n=46, 20.2 ± 0.3 y, initial VO2max = 32.1 ± 0.7 ml•kg−1•min−1, body fat = 25.7 ± 0.8%) completed a maximal graded cycle ergometer test and an acute HIIT exercise bout (HIIT challenge) before and after 4 weeks of HIIT. The HIIT challenge was an acute bout of eight 60‐sec cycling intervals at 100% of Wattsmax. The 4‐week HIIT consisted of 12 sessions (3 d•wk−1) of 8 to 12 cycling intervals at 100% of Wattsmax (60‐sec intervals; 75‐sec rest in between). Standard exercise‐related physiological variables were measured during the maximal cycle ergometer test and blood samples were collected at rest, immediately, and 30 min after completion of the HIIT challenge for analysis of inflammatory cytokines and markers of oxidative stress. Participants experienced 6% and 5% increases in VO2max and Wattsmax (both p≤0.001), respectively, after 4 weeks of HIIT. The post‐exercise blood lactate response was lower after 4 weeks of HIIT (p=0.0125), compared to before training. We also observed reductions in exercise heart rate and rating of perceived exertion at various submaximal cycling workloads (all p≤0.001) after training. Plasma IL‐6 increased immediately and 30 min after the HIIT challenge (p<0.0125), but 4 weeks of HIIT reduced this response (p<0.0125). IL‐8 and MCP‐1 increased in response to the HIIT challenge (both p≤0.001), but these responses were not altered by 4 weeks of HIIT. Before training, glutathione peroxidase (GPx) activity and malondialdehyde (MDA) levels increased (p=0.020 and p<0.001, respectively), but superoxide dismutase (SOD) activity was unchanged 30 min after the HIIT challenge. However, 4 weeks of HIIT further augmented GPx activity by 8% (p=0.026), attenuated MDA levels by 60% (p<0.001), and tended to increase SOD activity by 20% (p=0.059), in response to the HIIT challenge. In conclusion, 4 weeks of HIIT improves fitness and cycling exercise performance, and moderates the systemic inflammatory and oxidative stress responses to an acute bout of HIIT in sedentary men and women.Support or Funding InformationDole Foods, Inc., Westlake Village, CA
Exercise Increases Brain‐Derived Neurotrophic Factor in Serum Exosomes
Authors: Saengsawang Witchuda , Kongoun Sasithorn , Chanda Metha 
Published: November 2023

Brain Derived Neurotrophic Factor (BDNF) is a major neurotrophic factor that elicits several important roles in the nervous system including neuronal development, synaptic plasticity and neuronal survival. It is known that BDNF can be detected in blood circulation and its level is altered during exercise. However, which form of BDNF and how BDNF is released from the brain into blood circulation during exercise are still unknown. Exosomes are small vesicles secreted from cells and carry a number of molecules from one cell to another. Several studies showed that exosomes carry several neuronal proteins and are able to cross blood‐brain barrier. However, it is unknown whether BDNF is present in the exosomes. In the present study, we demonstrated that the truncated form of BDNF was detected in the exosomes isolated form blood obtained from the jugular vein of the horses. In addition, we found that the level of truncated BDNF was significantly higher in the exosomes obtained from the serum of active horses compared to the sedentary horses. These results suggested the possibility that truncated‐BDNF was secreted from the brain into blood circulation through the exosomes. This is the first study demonstrating the presence of truncated BDNF in the serum exsosomes. It also showed the effect of exercise on the level of truncated‐BDNF in serum exosomes. The knowledge can be applied for a better understanding on the roles of BDNF in exercise, as well as in several neurodegenerative diseases, which are related to changes in the level of BDNF.Support or Funding InformationThis work was supported by a grant from the Thailand Research Fund (TRF) to WS (TRG5880104). We also gratefully acknowledge support from the Faculty of Science, Mahidol University (to WS).
Troponin degradation products: more specific marker for myocardial infarction
Authors: Zahran Somaya , Figueiredo Vivian , Cembrowski George , Graham Michelle , Schulz Richard , Hwang Peter 
Published: November 2023

IntroductionMyocardial infarction (MI) is the death of cardiac muscle in the setting of severe ischemia (lack of oxygen and nutrient supply). Assay of serum troponin I (TnI) is the biochemical gold standard for detecting MI. With the development of high sensitivity assays, TnI is being detected in milder conditions such as reversible tachycardia or myocardial ischemia in the absence of radiologic evidence for infarct. Different types of MI are classified clinically: type 1 MI being the classic “heart attack” where the irreversible infarct necessitates a timely intervention. In contrast, type 2 MI is precipitated by a physiologic stressor (e.g. tachyarrhythmia, sepsis, or anemia) that causes ischemia in vulnerable regions of the heart. It is very important to differentiate irreversible infarct from reversible ischemia with a novel biomarker because the treatments are very different.RationaleWhile the mechanisms leading to TnI release are poorly understood, it is generally accepted that intracellular proteases are differentially activated in ischemia and in cell death. Cardiac TnI has intrinsically disordered N‐ and C‐terminal ends that are exposed and vulnerable to proteolytic digestion. TnI proteolysis products may be more rational and specific markers for irreversible cardiomyocyte death than its total level in the blood.MethodsWe collected blood samples from 29 hospitalised patients with elevated cTnI. We quantitated proteolytic degradation using sandwich ELISAs to specifically detect the N‐terminal, core, or C‐terminal regions of TnI using commercial antibodies (M18, MF4, and 560, respectively).ResultsWe observed a wide variation in the degree of proteolytic degradation of TnI across the patients' samples. Interestingly, degradation of TnI at both N‐ and C‐termini in type 1 MI samples was detected. However, the C‐terminus degradation was more robust, consistent and proportional to the severity of the infarct. On the other hand, there was less degradation observed in type 2 MI samples, indicating that TnI is released in a more intact form.ConclusionsProteolytic degradation of TnI at its C‐terminus is a more specific marker for clinically significant MI than total TnI level. Making a distinction between intact and degraded forms of TnI may be useful for identifying patients with focal infarct in need of urgent revascularization and monitoring intracellular proteolysis as a possible target for therapeutic intervention.Support or Funding InformationThis work was funded by the University of Alberta Hospital Foundation, CIHR, startup funds from the Department of Medicine and Faculty of Medicine & Dentistry in the University of Alberta, and the Hwang Professional Corporation
Non‐invasive Vagus Nerve Stimulation Acutely Improves Blood Pressure Control in a Placebo Controlled Study
Authors: Sabino‐Carvalho Jeann L , Antonino Diego , Teixeira André L , Maia‐Lopes Paulo M , Murray Aaron R , Deuchars Jim , Vianna Lauro C 
Published: November 2023

BackgroundDespite positive outcomes across a variety of disease states, invasive vagus nerve stimulation (VNS) has been associated with adverse side‐effects. Given this, non‐invasive VNS (tVNS) via the auricular branch of the vagus nerve (ABVN) has been proposed as an alternative approach. However, the mechanisms underlying these positive outcomes remain unclear. Therefore, we controlled the sensory effects (placebo) to investigate if tVNS acutely improves blood pressure (BP) control.MethodsThirteen healthy men (23±1yrs) were randomized across three experimental visits in a random order. In active tVNS, electrodes were placed on the tragus of the ear and electrical current was applied by using a Transcutaneous Electrical Nerve Stimulation device. A time‐ control visit was performed with the electrodes placed on tragus, but no current was applied (sham‐T). Additionally, to avoid a confounding sensory effect, another sham protocol was performed with same electrical current of the active visit, but the electrodes were placed on the ear lobe (an area without cutaneous nerve endings from the vagus – sham‐L). Before interventions were applied, we inform to subjects that both active tVNS and sham‐L would not cause any harm. Beat‐to‐beat heart rate (HR) and BP were monitored at rest, during tVNS (active, sham‐T and sham‐L) and recovery. Spontaneous cardiac baroreflex sensitivity (cBRS) was measured via sequence technique. Both HR (LF/HF) and BP variability (BPV) were also measured.ResultsArterial BP and BPV were not affected by any active or sham protocols (P>0.05). HR and LF/HF ratio decreased (Δ–3.4±1% and Δ–17±10%, P<0.05, respectively) and cBRS increased (Δ20±7%, P<0.05) only during active tVNS, but were unchanged during both sham protocols (P>0.05).ConclusionThe results of the present study provide evidence that tVNS acutely improves neural control of BP in healthy young men. These findings allow us to suggest that spontaneous cBRS and cardiac sympathovagal balance could play a role in the mechanisms involved in previously reported beneficial outcomes caused by tVNS. Future studies are needed to confirm these findings in older and diseased populations.Support or Funding InformationJ.L.S., A.L.T., P.M.M. have been supported by scholarships from Coordination for the Improvement of Higher Education Personnel (CAPES).
Impact of placental ischemia on cardiac structure and function during pregnancy and Post‐Partum
Authors: Bakrania Bhavisha , Granger Joey P. 
Published: November 2023

Preeclampsia (PE) is a disorder prevalent in 5–7% of pregnancies. It is characterized by maternal hypertension and endothelial dysfunction. PE is thought to develop in response to impaired spiral artery remodelling of the placenta, which leads to placental ischemia and ultimately the release of anti‐angiogenic and pro‐inflammatory factors into the maternal circulation. More recently, it has been shown that cardiac function is impaired in women with PE, including hypertrophy and, systolic and diastolic dysfunction, with symptoms persisting one year post‐partum. In addition to the significant health risks imposed during pregnancy, multiple studies report increased risk of cardiovascular disease for mother and baby later in life. The placental factors, sFlt‐1 and TNF‐α, have been shown to play a role in cardiac dysfunction and the structural abnormalities seen during PE, however, the mechanisms remain unclear. Therefore, it is important to utilise an appropriate model of PE to assess cardiac function and investigate mechanisms of cardiac dysfunction, such as the Reduced Uterine Perfusion Pressure (RUPP) model, where silver clips are placed on the abdominal aorta and branches of the ovarian arteries to induce placental ischemia. We have previously reported that the RUPP model has many of the characteristics seen in women with PE. The aim of this study was to assess cardiac structure and function in RUPP rats during pregnancy and post‐partum to discern any similarities to the human condition. A normal pregnant (NP, n=8) and RUPP (n=8) group was included in this study. The RUPP group underwent surgery on gestational day (GD) 14 for placement of silver clips. Both the NP and RUPP rats had carotid catheters placed on GD 18, and all initial blood pressure and echocardiography measurements were made on GD 19. A second echocardiography analysis was performed 3 months post‐partum. The RUPP group had significantly increased mean arterial pressure compared to the NP group on GD 19 (123 ± 3 vs. 97 ± 2 mmHg, P<0.01). RUPP hearts also showed reductions in ejection fraction (60 ± 2 vs. 78 ± 2 %, P<0.01) and fractional shortening (46 ± 3 vs. 56 ± 1 %, P=0.05), in addition to cardiac hypertrophy (0.97 ± 0.04 vs.0.91 ± 0.02 g, P=0.02). Interestingly, systolic dysfunction was persistent post‐partum in RUPP hearts, where ejection fraction (67 ± 3 vs.76 ± 2 %, P<0.01) and fractional shortening (50 ± 5 vs. 56 ± 2 %, P=0.05) remained impaired. In conclusion, cardiac dysfunction is present in the RUPP model during pregnancy and post‐partum. Therefore, this model could be useful in understanding the mechanisms which underpin the cardiac structural and functional abnormalities seen in PE patients.Support or Funding InformationThis study was funded by the NIH (HL51971).
Endothelin receptor type B (ETB)‐deficient pregnant rats have exaggerated placental ischemia‐induced hypertension
Authors: Dent Edward Alexander , Spradley Frank Travis , Granger Joey P 
Published: November 2023

Preeclampsia (PE) is a pregnancy‐specific disorder of new‐onset hypertension that threatens the lives of both mother and fetus. While the pathogenesis of PE is unclear, studies have implicated placental ischemia. Indeed, reduced uterine perfusion pressure (RUPP)‐induced placental ischemia in experimental animals stimulates the release of soluble factors into the maternal circulation, causing vascular dysfunction and hypertension. Pharmacological blockade of the vasoconstrictive endothelin type A receptor (ETA) abolishes RUPP‐induced hypertension. Although blockade of vasodilatory ETB receptors increases blood pressure during late pregnancy in rodents and placental ischemia has been shown to reduce ETB receptor expression, the importance of the ET/ETB receptor pathway in blood pressure regulation during pregnancy or in response to placental ischemia is unclear. Therefore, we tested the hypothesis that ETB deficiency results in exaggerated placental ischemia‐induced hypertension. At eighteen weeks old, ETB deficient (def) and transgenic control (Tg) timed‐pregnant rats were generated using Wistar Hannover males. Rats underwent RUPP or Sham surgeries at gestational day 14, with assessment of mean arterial blood pressure (MAP, carotid catheter) and pregnancy weights and plasma collection at day 19. This resulted in 4 groups: Sham Tg (N=13); RUPP TG (N=10); Sham ETB def (N=11); and RUPP ETB def (N=6). MAP was greater in Sham ETB def compared to Sham Tg (109±3 vs. 79±3 mmHg, P<0.05). MAP levels were increased by RUPP in both Tg (99±3 mmHg, P<0.05) and ETB def (139±6 mmHg, P<0.05), but the degree of this RUPP hypertension was exaggerated in ETB def rats (30 vs. 20 mmHg). Average fetal weights were lower in Sham ETB def than Sham Tg (1.79±0.11 vs. 2.24±0.06 g, P<0.05) and were reduced by RUPP in Tg (2.08±0.06 g, P<0.05) but not further reduced in RUPP ETB def (1.66±0.13 g). Average placental weights were similar in Sham ETB def and Sham Tg (0.52±0.01 vs. 0.50±0.01 g). RUPP reduced placental weights in Tg (0.43±0.03 g, P<0.05) but not RUPP ETB def (0.55±0.04 g). Placental sufficiency (fetal weight divided by placental weight, a marker of placental nurturing capacity) was lower in Sham ETB def compared to Sham Tg (4.05±0.15 vs. 4.58±0.20, P<0.05). This was not reduced by RUPP in Tg (4.41±0.36) but was further reduced in RUPP ETB def (3.11±0.38, P<0.05). Circulating levels of cGMP, a surrogate measure of bioavailability of the vasodilatory nitric oxide (NO), were reduced in Sham ETB def compared to Sham Tg (43±5 vs. 178±18 pg/mL, P<0.05), which were reduced by RUPP in Tg (18±3 pg/mL), but not further reduced in RUPP ETB def (35±11 pg/mL). In conclusion, these data not only suggest an important role for ETB in blood pressure regulation during normal pregnancy but also in buffering the response to placental ischemia‐induced hypertension.Support or Funding InformationK99HL130577, HL51971, P20GM104357