scholarly journals Effects of Gancao Nourish Yin Decoration on Liver Metabolic Profiles in hTNF-α Transgenic Arthritic Mouse Model

2020 ◽  
Author(s):  
RongBin Pan ◽  
Kok Suen Cheng ◽  
Yanjuan Chen ◽  
Xingwang Zhu ◽  
Wenting Zhao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Pantothenic Acid ◽  
Human Tumor ◽  
Sugar Metabolism ◽  
Amino Sugar ◽  
Control Group ◽  
Therapeutic Effects ◽  
Metabolic Profiles ◽  
Necrosis Factor Alpha ◽  
Arthritic Mouse

Abstract BackgroundGancao Nurish Yin (GCNY) decoction has been applied to clinical rheumatoid arthritis (RA) patients and it had shown effectiveness not only in disease activity controlling but also on improving patients’ physical status. However, its mechanism of function has not been investigated. Metabolic perturbations have been associated with RA and targeting the metabolic profile is one of the ways to manage the disease. The aim of this study was to observe the effect of GCNY on metabolic changes of human tumor necrosis factor alpha (hTNF-α) transgenic arthritic mouse model. MethodshTNF-α transgenic arthritic model mice were divided into control and GCNY groups with 6 mice in each group. After 8 weeks of treatment, liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry (LC/MS) analysis. Significantly regulated metabolites by GCNY treatment were first identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analysis.ResultsOf the 126 metabolites detected in the liver, 17 metabolites were with significantly altered between control group mice and mice treated with GCNY. Specifically, thiamine, gamma-L-Glutamyl-L-valine, pantothenic acid, pyridoxal (Vitamin B6), succinic acid, uridine 5'-diphospho-glucuronic acid (UDP-D-Glucuronate), uridine, allantoic acid, N-Acetyl-D-glucosamine, nicotinamide ribotide and N2,N2-Dimethylguanosine were down-regulated by GCNY treatment whereas isobutyrylglycine, N-Acetylcadaverine, N-Carbamoyl-L-aspartic acid, L-Anserine, creatinine and cis-4-Hydroxy-D-proline were up-regulated. Six metabolic pathways were significantly altered including the alanine, aspartate and glutamate metabolism, pyrimidine metabolism, thiamine metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and CoA biosynthesis and citrate cycle (TCA cycle). Integrative metabolic network analysis suggested the possibility of GCNY having both positive and negative effects on RA through the suppression of angiogenesis and promotion of leukocyte extravasation into the synovium, respectively. ConclusionsGCNY can induce a change in the metabolic profiles of hTNF-α transgenic arthritic mouse model. Further optimization of this decoction may lead to better therapeutic effects on RA patients.

scholarly journals Xiangshao Granule Exerts Antidepressive Effects in a Depression Mouse Model by Ameliorating Deficits in Hippocampal BDNF and TrkB

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yi Chen ◽  
Jie Liu ◽  
Xiaoting Wu ◽  
Edouard Collins Nice
Keyword(s):  
Treatment Group ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Open Field Test ◽  
The Body ◽  
Control Group ◽  
Therapeutic Effects ◽  
Model Group ◽  
Depression Group ◽  
Antidepressive Effects

This study explores the therapeutic effects of Xiangshao granules in a mouse depression model and examines the potential molecular mechanisms involved. After 21 consecutive days of chronic stress challenge, all mice were divided into three groups: control group, depression group, and Xiangshao granule treatment group. On the 22nd day, rats in the Xiangshao granule treatment group received Xiangshao granules via gastrogavage for 3 consecutive weeks. Depression group mice showed a significant reduction of crossings (P<0.01) but not rearings (P<0.05). Serum CRH, CORT, and ACTH levels were significantly increased in depression mice compared with control (P<0.05) and the expression levels of hippocampal BDNF and TrkB were reduced in the model group (P<0.05). However, Xiangshao granule treatment remarkably rescued the decrease in the body weight (P<0.05), increased crossings in the open field test (P<0.05), upregulated the expression of hippocampal BDNF and TrkB expression, and reduced the serum CRH, CORT, and ACTH concentrations compared with the depression group (P<0.05). Collectively, these results demonstrated that Xiangshao granule could effectively induce antidepressive effects in the depression mouse model by ameliorating the expression of hippocampal BDNF and TrkB.

scholarly journals A Novel Standardized Method of Renal Biopsy in Mice

2021 ◽  
pp. 1-9
Author(s):  
Xinyue Mao ◽  
Chang Wang ◽  
Zhihui Xu ◽  
Yixin He ◽  
Yanpei Hou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Renal Biopsy ◽  
Weight Ratio ◽  
Control Group ◽  
Tubular Damage ◽  
Therapeutic Effects ◽  
Minimal Trauma ◽  
Significant Difference ◽  
Renal Biopsies ◽  
Standardized Method

Introduction: In animal models, it can be difficult to confirm therapeutic effects due to technical inconsistencies and other reasons. Although renal biopsy is widely used in clinical diagnosis, it is rarely used in animal experimental models, especially in mice, because the problems of surgery-induced renal injury and bleeding have not been solved. Methods: We developed an easy-to-use method of renal biopsy in mice and evaluated whether 3 consecutive renal biopsies can be performed in the same kidney in a standardized manner. This method was verified using 2 mouse models, a healthy mouse model and a unilateral ureteral obstruction (UUO) mouse model, and evaluated based on renal function and histological changes. Results: There were no perioperative complications in any of the model mice. There was no significant difference in serum Cr, 24-h urine protein, or kidney/body weight ratio between the biopsy and control groups. Each biopsy sample contained sufficient renal tissue. The damage to the operated tissue was limited to the tissue near the biopsy site. Compared with renal tissues in the corresponding control group, the renal tissues obtained from the 3 biopsies (healthy model days 0, 4, and 7 and UUO model days 3, 7, and 10) and the remnant renal tissues after the biopsy showed no significant difference in the glomerular sclerosis index, degree of renal tubular damage, inflammatory response and renal fibrosis in these 2 models. Conclusions: Our new standardized method of renal biopsy in mice is a safe and cost-saving approach that allows repeated renal biopsies and ensures minimal trauma and sufficient sample size to quality in experimental disease models.

scholarly journals The Anti-Inflammatory Effect of Hydrogen Gas Inhalation and Its Influence on Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 22 (21) ◽  
pp. 12049
Author(s):  
I-Chia Liang ◽  
Wen-Chin Ko ◽  
Yu-Jou Hsu ◽  
Yi-Ru Lin ◽  
Yun-Hsiang Chang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Mrna Expression ◽  
Choroidal Neovascularization ◽  
Hydrogen Gas ◽  
Age Related Macular Degeneration ◽  
Fluorescence Angiography ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Age Related

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. Methods: Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. Results: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. Conclusion: H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.

scholarly journals Serum Metabolomic Profiling Reveals the Amelioration Effect of Methotrexate on Imiquimod-Induced Psoriasis in Mouse

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiaxin Zong ◽  
Jieyi Cheng ◽  
Yuanfeng Fu ◽  
Jing Song ◽  
Weisong Pan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inositol Phosphate ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Glutathione Metabolism ◽  
Control Group ◽  
Therapeutic Effects ◽  
Serum Samples ◽  
Galactose Metabolism ◽  
Metabolomics Data

Background:The imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model.Methods:Male BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites.Results:It was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group.Conclusion:The differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.

Effect of Chinese Herbal Monomer Hairy Calycosin on Nonalcoholic Fatty Liver Rats and its Mechanism

2019 ◽  
Vol 22 (3) ◽  
pp. 194-200 ◽  
Author(s):  
Xiang Liu ◽  
Zhi-Hong Xie ◽  
Chen-Yuan Liu ◽  
Ying Zhang
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Liver Homogenate ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Chinese Herbal ◽  
Tnf Α ◽  
Model Control

Background: Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali. Aims and Scope: The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats. Materials and Methods: 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively. Results: Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller. Conclusion: Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

scholarly journals Effects and Responsiveness of a Multicomponent Intervention on Body Composition, Physical Fitness and Leptin in Overweight/Obese Adolescents

2021 ◽  
Vol 18 (14) ◽  
pp. 7267
Author(s):  
Leticia Borfe ◽  
Caroline Brand ◽  
Letícia Schneiders ◽  
Jorge Mota ◽  
Claudia Cavaglieri ◽  
...  
Keyword(s):  
Body Composition ◽  
Physical Fitness ◽  
Intervention Group ◽  
Interleukin 10 ◽  
Control Group ◽  
Post Intervention ◽  
Necrosis Factor Alpha ◽  
Obese Adolescents ◽  
Quasi Experimental ◽  
Multicomponent Program

Physical exercise reduces the biochemical markers of obesity, but the effects of multicomponent interventions on these markers should be explored. The present study aimed to elucidate how overweight/obese adolescents respond to a multicomponent program approach on body composition, physical fitness, and inflammatory markers, using a quasi-experimental study with 33 overweight/obesity adolescents (control group (CG) = 16; intervention group (IG) = 17). The intervention consisted of 24 weeks with physical exercises and nutritional and psychological guidance. Both groups were evaluated at the pre/post-intervention moments on body mass index (BMI); body fat (%Fat); waist circumference (WC); waist/hip ratio (WHR); waist-to-height ratio (WHtR), cardiorespiratory fitness (CRF); abdominal strength, flexibility; leptin; interleukin 6; interleukin 10; and tumor necrosis factor-alpha. Mixed-analysis of variance and generalized estimation equations were used for statistical analysis. There was an interaction effect between groups and time on %Fat (p = 0.002), WC (p = 0.023), WHR (p < 0.001), WHtR (p = 0.035), CRF (p = 0.050), and leptin (p = 0.026). Adolescents were classified as 82.4% responders for %Fat, 70.6% for WC, 88.2% for WHR, and 70.6% for CRF. Further, there was an association between changes in %Fat (p = 0.033), WC (p = 0.032), and WHR (p = 0.033) between responders and non-responders with CRF in the IG. There was a positive effect on body composition, physical fitness, and leptin. In addition, reductions in body composition parameters were explained by CRF improvements.

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