scholarly journals Substance P Enhances Doxorubicin (Adriamycin)-associated Autophagy and Reduces Cardiomyocyte Apoptosis.

2021 ◽  
Author(s):  
Fa-Xiu Chen ◽  
Jian Hu ◽  
Jing Fang ◽  
Qing-Ling Li ◽  
Qin Wan ◽  
...  
Keyword(s):  
Substance P ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Sensory Nerves ◽  
Control Group ◽  
Model Group ◽  
Organ Systems ◽  
Wide Range ◽  
Group A ◽  
Antagonist Group

Abstract BackgroundAnthracyclines, including doxorubicin, are some of the most potent anticancer drugs available. However, the use of doxorubicin as a chemotherapeutic agent is severely hindered by dose-limiting toxicity, particularly cardiotoxicity, while degrading other organ systems. Despite years of use and the number of details published on this drug, the understanding of its cellular mechanisms remains limited. MethodCardiomyocyte grouping was carried out, where H9C2 cardiomyocytes were randomly divided into a control group, a myocardial model group, an SP group, and an SP antagonist group. For replication in animal models, twelve rats were similarly randomly assigned into a control group, a myocardial model group, an SP group, and an SP antagonist group. Except for the control group, the rats in the other groups were modelled: the rats were injected with adriamycin solution. Flow cytometry was used to detect apoptosis, while HE staining, TUNEL stain, Western Blot detection, and transmission electron microscopy were performed to detect autophagy levels accordingly. All the results were analysed and carefully interpreted. Resultshe tachykinin, substance P, is located mainly in sensory nerves and in the heart, where substance P-containing nerve fibres are often found around coronary vessels, making them ideally situated to detect changes in the myocardial environment. Apoptosis and autophagy are genetically regulated, evolutionary-conserved processes that regulate cell fate and are important for development, normal physiology, and a wide range of diseases. Recent studies show that despite the significant differences between these two processes, their regulation is closely connected and certain regulators are able to control both apoptosis and autophagy. ConclusionsIn this study, the influence of substance P was discussed, providing possible molecular mechanisms for crosstalk between apoptosis and autophagy mediating heart failure due to doxorubicin therapy. Trial registration(20192BBGL7D031) 2019-09-17.

scholarly journals A Study of the Molecular Mechanism by Which Substance P Enhances Doxorubicin (Adriamycin)-Associated Autophagy and Apoptosis of Cardiomyocytes Induces Heart Failure

2021 ◽  
Author(s):  
Fa-Xiu CHEN CHEN ◽  
Jian Hu ◽  
Jing Fang ◽  
Qing-Ling Li ◽  
Qin Wan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Substance P ◽  
Molecular Mechanisms ◽  
Sensory Nerves ◽  
Control Group ◽  
Model Group ◽  
Organ Systems ◽  
Wide Range ◽  
Group A ◽  
Antagonist Group

Abstract Background: Anthracyclines, including doxorubicin, are some of the most potent anticancer drugs available. However, the use of doxorubicin as a chemotherapeutic agent is severely hindered by dose-limiting toxicity, particularly cardiotoxicity, while degrading other organ systems. Despite years of use and the amount of details published on this drug, the understanding of its cellular mechanisms is still incomplete. Method: Cardiomyocyte grouping was carried out, where H9C2 cardiomyocytes were randomly divided into a control group, a myocardial model group, an SP group and an SP antagonist group. For replication in animal models, twelve rats were similarly divided randomly into a control group, a myocardial model group, an SP group, and an SP antagonist group. Except for the control group, the rats in the other groups were modelled: the rats were injected with adriamycin solution. Flow cytometry was used to detect apoptosis, while HE staining, TUNEL stain, Western Blot detection and transmission electron microscopy were performed to detect autophagy levels accordingly. All the results were analysed and carefully interpreted. Results: The tachykinin, substance P, is located mainly in sensory nerves and in the heart, where substance P-containing nerve fibres are often found around coronary vessels, making them ideally situated to detect changes in the myocardial environment. Apoptosis and autophagy are genetically-regulated, evolutionary-conserved processes that regulate cell fate and are both important for development, normal physiology, and a wide range of diseases. Recent studies show that despite the significant differences between these two processes, their regulation is closely connected and certain regulators have been found to be able to control both apoptosis and autophagy. Conclusions: In this study, the influence of substance P was discussed, providing possible molecular mechanisms for crosstalk between apoptosis and autophagy mediating heart failure due to Doxorubicin therapy. Trial registration: (20192BBGL7D031) 2019-09-17.

scholarly journals Genomic analyses reveal a conserved glutathione homeostasis pathway in the invertebrate chordate Ciona intestinalis

2009 ◽  
Vol 39 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Gerardo M. Nava ◽  
David Y. Lee ◽  
Javier H. Ospina ◽  
Shi-Ying Cai ◽  
H. Rex Gaskins
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Ciona Intestinalis ◽  
Phylogenetic Position ◽  
Filter Feeder ◽  
Diverse Range ◽  
Regulatory Pathways ◽  
Wide Range ◽  
Redox Buffer ◽  
Invertebrate Chordate

The major thiol redox buffer glutathione (l-γ-glutamyl-l-cysteinylglycine, GSH) is central to cell fate determination, and thus, associated metabolic and regulatory pathways are exquisitely sensitive to a wide range of environmental cues. An imbalance of cellular redox homeostasis has emerged as a pathologic hallmark of a diverse range of human gene-environment disorders. Despite the central importance of GSH in cellular homeostasis, underlying genetic regulatory pathways remain poorly defined. This report describes the annotation and expression analysis of genes contributing to GSH homeostasis in the invertebrate chordate Ciona intestinalis . A core pathway comprising 19 genes contributing to the biosynthesis of GSH and its use as both a redox buffer and a conjugate in phase II detoxification as well as known transcriptional regulators were analyzed. These genes exhibit a high level of sequence conservation with corresponding human, rat, and mouse homologs and were expressed constitutively in tissues of adult animals. The GSH biosynthetic genes Gclc and Gclm were also responsive to the prototypical antioxidant tert-butylhydroquinone. The present evidence of a conserved GSH homeostasis pathway in C. intestinalis together with its phylogenetic position as a basal chordate and lifestyle as a filter feeder constantly exposed to natural marine toxins introduces this species as an important animal model for defining molecular mechanisms that potentially underlie genetic susceptibility to environmentally associated stress.

scholarly journals Effect of Malus halliana Koehne Polysaccharides on Functional Constipation

2018 ◽  
Vol 16 (1) ◽  
pp. 956-962 ◽  
Author(s):  
Yingying Niu ◽  
Junya Wang ◽  
Pengyu Wang ◽  
Xiuchun Guo ◽  
Jinmei Wang ◽  
...  
Keyword(s):  
Substance P ◽  
Moisture Content ◽  
Dose Group ◽  
Low Dose ◽  
Functional Constipation ◽  
Positive Control ◽  
Positive Control Group ◽  
Control Group ◽  
Group Model ◽  
Model Group

AbstractThe effects of Malus halliana Koehne polysaccharides on functional constipation was investigated in this study. The rats were divided into six groups: normal group, model group, positive control group, M. halliana polysaccharides high dose groups 1200 mg/ kg, medium dose groups 1000 mg/ kg and low dose groups 800 mg/kg. The model of constipation was established by loperamide hydrochloride. Feces weight at 6 and 24 hours after treatment, Colon moisture content, in addition the levels of motilin (MTL), gastrin (Gas), somatostatin (SS), substance P (SP) in serum were used to evaluate the preventive effects of M. halliana polysaccharides on constipation. Compared with the model group, the positive control group, M. halliana polysaccharide high, medium and low dose group 6 h weight of feces, colon moisture content, the levels of motilin (MTL), gastrin (GAS) and substance P(SP) significantly (p <0.01) increased, the levels of somatostatin (SS) significantly decreased. The results indicated that the high, middle and low dosage of M. halliana polysaccharide could effectively improve functional constipation. Amongst these doses, the low dose group was better than others.

The Effects of Moxibustion on Serum Interleukins and T Cell Subset in H.polyri Infected Rats

2015 ◽  
Vol 3 (1) ◽  
pp. 38-45
Author(s):  
Jing Shen ◽  
Yan Peng ◽  
Dong-Mei Shi ◽  
Yin-Shuai Feng ◽  
Yan-Ling Hou ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Control Group ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Model Group ◽  
Tnf Α ◽  
Group A ◽  
Histomorphological Changes ◽  
Group B ◽  
Group D

Abstract Objective: to observe the effects of moxibustion on histomorphological changes of gastric mucosa, as well as on serum IL-6、IL-8、TNF-α，Hp IgG、CD3+、CD4+、CD8+ in helicobacter pylori (Hp) infected rats, so that to better understand how the moxibustion repairs the Hp- induced gastric mucosal injury. Methods: 40 SD rats were randomly assigned to four groups: group A (blank control), group B (Hp infection model), group C (moxibustion plus model), group D (electro-acupuncture plus model), 10 for each group. The “NaHCO3 plus Indometacin and Hp intragastric administration” method was employed to make gastritis model. Acupoints selected for “repair” purpose were Zu San Li (ST36), Zhong Wan (CV12), Guan Yuan (RN4), Pi Shu (BL20), Wei Shu(BL21). The histomorphological changes of gastric mucosa in rats were observed under light microscope after HE stain; IL-6, IL-8, TNF-α, Hp IgG values were evaluated by ELISA method; values of CD3+、CD4+、CD8+、CD4+/CD8+ were measured by flow cytometry method. Results: compared with group A, the values of IL-6, IL-8, TNF-α, Hp IgG and CD8+ in group B were increased（P＜0.01）, whereas the values of CD3+、CD4+、CD4+/CD8+ were decreased（P＜0.01）. Compared with group B, the values of IL-8（P＜0.05）,TNF-α（P＜0.05）, IL-6（P＜0.01）, Hp IgG（P＜0.01） and CD8+ （P＜0.05） in group C were decreased, whereas the values of CD3+（P＜0.05）,CD4+（P＜0.05）,CD4+/CD8+ （P＜0.05） were increased, meanwhile such values in group D had no significant changes. Compared with group D, the values of IL-6（P＜0.05）,IL-8 （P＜0.05）and Hp IgG （P＜0.01）in group C were decreased, whereas CD4+/CD8+（P＜0.05）were increased, all those changes had statistical significance. Conclusion: the preventive and therapeutic effects of moxibustion on Hp related gastritis might be realized by two ways- to inhibit the secretion of proinflammatory cytokines such as IL-6, IL-8 and TNF-α, or to regulate the production of immune factors (such as up-regulation of CD3+, CD4+ and down-regulation of CD8+).

scholarly journals Effects of Yiqi Tongyang on HCN4 Protein Phosphorylation in Damaged Rabbit Sinoatrial Node Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-6
Author(s):  
Jinfeng Liu ◽  
Ruxiu Liu ◽  
Jie Peng ◽  
Yanli Wang
Keyword(s):  
Protein Expression ◽  
Protein Phosphorylation ◽  
Treatment Effects ◽  
Molecular Mechanisms ◽  
Sinoatrial Node ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Model Group ◽  
Sinoatrial Node Cells

The hyperpolarization-activated cyclic nucleotide-gated cation channel (If) is closely associated with sinoatrial node pacing function. The present study aimed to investigate the molecular mechanisms involved in pacing function improvements of damaged sinoatrial node cells and the consequent treatment effects on sick sinus syndrome (SSS) after the use of Yiqi Tongyang. HCN4 channel protein expression and phosphorylation were measured by immunoblotting and fluorescent quantitation. After ischemia-reperfusion injury (model group), the HCN4 protein and the optical density (OD) of the phosphorylated HCN4 protein as well as intracellular PKA activity in the sinoatrial node cells decreased significantly. However, the OD values and PKA activity increased to different degrees after treatment with serum containing different doses of Yiqi Tongyang; in contrast, no significant improvement was seen in the control group compared to the model group. These findings demonstrated that the use of the traditional Chinese medicine Yiqi Tongyang could increase HCN4 protein expression and phosphorylation as well as PKA activity within sinoatrial node cells damaged by ischemia-reperfusion. The HCN4 protein is involved in theIf-related ion channel. Here, we speculated that these effects could be associated with upregulation of HCN4 protein phosphorylation, which consequently improved cell automaticity, increased heart rate, and had treatment effects on SSS.

scholarly journals Dissecting the Roles of the Tuberin Protein in the Subcellular Localization of the G2/M Cyclin, Cyclin B1

2021 ◽  
Author(s):  
Jessica Dare-Shih ◽  
Adam Pillon ◽  
Jackie Fong ◽  
Elizabeth Fidalgo da Silva ◽  
Lisa Porter
Keyword(s):  
Cell Cycle ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Molecular Mechanisms ◽  
Cyclin B1 ◽  
Nuclear Accumulation ◽  
Benign Tumors ◽  
Tsc2 Gene ◽  
Organ Systems ◽  
Wide Range

Tuberin is a major component of the protein regulatory complex known as the Tuberous Sclerosis Complex and plays a crucial role in cell cycle progression and protein synthesis. Mutations in the Tuberin gene, TSC2, lead to the formation of benign tumors in many organ systems and causes the Tuberous Sclerosis Complex disorder. Genotypes ranging from point mutations to large deletions in the TSC2 gene have been clinically characterized with a wide range of phenotypes from skin tumors to large brain tumors. Our current work investigates the molecular mechanisms behind Tuberin and its ability to regulate the cell cycle through its binding to the G2/M cyclin, Cyclin B1. After creating an early stop codon in a critical region of the Tuberin, our results show the in vitro phenotype that occurs from a truncated Tuberin protein. Herein we demonstrate that this clinically relevant truncated form of Tuberin promotes an increased nuclear accumulation of Cyclin B1 and a subsequent increase in cell proliferation supporting the phenotypic data seen in the clinic with Tuberous Sclerosis Complex patients showing deletions within the TSC2 gene. This data provides an insight into some of the functional and molecular consequences of truncated proteins that are seen in clinical patients.

scholarly journals The Effect of Acupuncture to SP6 on Skin Temperature Changes of SP6 and SP10: An Observation of “Deqi”

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jia-Min Yang ◽  
Xiao-Yu Shen ◽  
Ling Zhang ◽  
Song-Xi Shen ◽  
Dan-Dan Qi ◽  
...  
Keyword(s):  
Skin Temperature ◽  
Saline Control ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Saline Control Group ◽  
Temperature Changes ◽  
Group A ◽  
Group B ◽  
The Relationship

Background. Deqi sensation is a complex but an important component for acupuncture effect. In this study, we tried to observe the relationship between Deqi and skin temperature changes and whether there was some relativity between Deqi and needle stimulations on cold congealing and dysmenorrhea rat model. Thirty-two female Sprague Dawley (SD) rats were randomly divided into four groups (Saline Control Group, Model Group, Group A with strong stimulation, and Group B with small stimulation). Group A and Group B were performed with different stimulations. We found that, compared with saline control group, model group, and Group B, Group A showed that the skin temperature changes on right acupoint SP6 and SP10 increased significantly at 5 min–10 min interval. The skin temperature changes on left SP6 decreased at instant–5 min interval. The skin temperature changes on right SP10 decreased significantly at instant–5 min interval and 10 min–20 min interval. Thermogenic action along Spleen Meridian of Foot Greater Yin was manifested as simultaneous skin temperature increase on right SP6 and SP10 at 5 min–10 min interval after needling SP6, which was helpful to illustrate the relationship between the characteristic of Deqi and needle stimulations.

scholarly journals The Roles of Skin Fibroblasts at Local Acupoints in Chrono-Acupuncture

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nannan Liu ◽  
Zhengyu Zhao ◽  
Qizhi Zhou ◽  
Xiaohong Zhang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acupuncture Treatment ◽  
Treatment Time ◽  
Subcutaneous Tissue ◽  
Acupuncture Group ◽  
Control Group ◽  
Model Group ◽  
Time Points ◽  
Group A ◽  
And Control ◽  
Time Point

Objective. The aim of this study was to demonstrate the peripheral mechanisms of chrono-acupuncture by observing acupuncture at different time points affecting relative proteins to regulate the cytoskeleton of fibroblasts differently. Methods. A total of 108 male SD rats (180–220 g) that have basic pain threshold within 3–10 s were selected and randomly divided into group A (n = 72) and control group (n = 36). After the succession of modeling with CFA injection, the rats in group A were randomly divided into model group and acupuncture group, each group containing 36 rats. Then according to the different treatment time, each group was randomly classified into 6 subgroups (ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20), each subgroup containing 6 rats (n = 6). On the second day of successful modeling, the rats in the acupuncture group received acupuncture treatment at the corresponding time point, while the control group and the model group were only tied up at the corresponding time point without any treatments. Methods of operation: use 0.5-inch needles, puncture the rats’ “Zusanli” on the affected limb, with Twirling manipulation for a minute after every five minutes; the treatment lasts thirty minutes in total. After 7 days of treatments, the skin and subcutaneous tissue of rats’ acupoint area of “Zusanli” on the affected limb were taken and then stained by immunofluorescence double staining method to observe the expression of the fibroblast cytoskeleton F-actin and β-tubulin under the LSCM while using western blot to observe the expression of P38MAPK/P-P38MAPK. Results. The expression of the cytoskeleton F-actin and β-tubulin at acupoint area in the acupuncture group was significantly higher than that in the control and model group. The effect of acupuncture on the restructure of the fibroblast cytoskeleton is different at different time points, the most effective time point was at ZT12 while the least at ZT16. Acupuncture can decrease the high expression of P-P38MAPK/P38MAPK in the model group, and the effect has time differences. The expression of P-P38MAPK/P38MAPK increased more significantly at ZT16 than ZT12. Conclusion. The remodeling difference of fibroblast cytoskeleton after receiving acupuncture treatment could be one of the peripheral bases of the chrono-acupuncture.

Ovarian toxicity in rats caused by methidathion and ameliorating effect of vitamins E and C

2007 ◽  
Vol 26 (6) ◽  
pp. 491-498 ◽  
Author(s):  
Mehmet Güney ◽  
Hilmi Demirin ◽  
Baha Oral ◽  
Meltem Özgüner ◽  
Gökhan Bayhan ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Body Weight ◽  
Molecular Mechanisms ◽  
Corn Oil ◽  
Ovarian Follicles ◽  
Control Group ◽  
Ovarian Toxicity ◽  
Vitamins E And C ◽  
Group A ◽  
Ovarian Damage

We have investigated the effect of subchronic administration of methidathion (MD) on ovary evaluated ameliorating effects of vitamins E and C against MD toxicity. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD + Vit group). MD and MD + Vit groups were given MD by gavage five days a week for four weeks at a dose level of 5 mg/kg/day by using corn oil as the vehicle. Serum malondialdehyde (MDA: an indicator of lipid peroxidation) concentration, serum activity of cholinesterase (ChE), and ovary histopathology were studied. The level of MDA increased significantly in the MD group compared with the control ( P < 0.005). Serum MDA decreased significantly in the MD + Vit group compared with the MD group ( P < 0.05). The activities of ChE decreased significantly both in the MD and MD + Vit groups compared with the controls ( P < 0.05). However, the decrease in the MD + Vit groups was less than in the MD group; the ChE activity in the MD + Vit group was significantly higher compared with MD group ( P < 0.05). Number of ovarian follicles were significantly lower in the MD group compared to the controls ( P < 0.05). Number of atretic follicles were significantly higher in the MD group than in the controls ( P < 0.05). Follicle counts in MD + Vit group showed that all types of ovarian follicles were significantly higher, and a significant decrease in the number of atretic follicles compared with the MD group ( P < 0.05). In conclusion, subchronic MD administration caused an ovarian damage, in addition, LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Treatment with vitamins E and C after the administration of MD reduced LPO and ovarian damage. Human & Experimental Toxicology (2007) 26, 491—498

scholarly journals Comparison of effectiveness of Salvadora Persica whitening toothpaste with commercial whitening toothpaste at removing stain

2009 ◽  
Vol 21 (3) ◽  
Author(s):  
Erlina Sih Mahanani ◽  
Erry Mochamad Arief ◽  
Samantha Victoria Samuel
Keyword(s):  
Drinking Water ◽  
Artificial Saliva ◽  
Visual Assessment ◽  
Control Group ◽  
Salvadora Persica ◽  
Stain Removal ◽  
Wide Range ◽  
Group A ◽  
Group B ◽  
Comparison Of Effectiveness

The miswak, a traditional chewing stick for cleaning teeth, is made from the plant Salvadora persica. It contains a wide range of healthy components in maintaining good oral hygiene. The objective of this study is to determine the effectiveness of whitening toothpaste containing Salvadora persica extract at removing tea and chlorhexidine stain by comparing with one of commercially available whitening toothpaste and drinking water as a control group. A randomized experimental study was done. The standard method cycled clear acrylic specimens through artificial saliva, 0.2% chlorhexidine and tea on the hour 8 times per day and stain were measured using a spectrophotometer to achieve baseline reading. Test interventions were 2 whitening kinds of toothpaste; whitening toothpaste containing Salvadora persica extract (group A), commercial whitening toothpaste (group B) and drinking water as a control group (group C). Treatment interventions were done at 09:00 and 16:00 by exposing the specimens to slurries of each treatment for 2 minutes. The specimens remained in the artificial saliva between each cycles day and night. At the end of the day, the stain was assessed by spectrophotometer and Lobene Stain Index. The comparison of total stain removal assessed by spectrophotometer on day 5 between all groups was significant (p=0.007). The median of total stain removal and visual assessment recording using Lobene stain index showed Salvadora persica whitening toothpaste scored more reduction of staining followed by commercial whitening toothpaste and then control group. As a conclusion, the whitening toothpaste containing Salvadora persica is more effective at removing tea and chlorhexidine stain.

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