scholarly journals Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

Author(s):  
Yinlan Xu ◽  
Shuangxiu Wan ◽  
Panpan Sun ◽  
Ajab Khan ◽  
Jianhua Guo ◽  
...  

Abstract Background PCV2 (Porcine circovirus type 2) is one of the major pathogens commonly in pigs, which can cause immunosuppression and apoptosis. Vaccinations and single drugs are not totally prevent and treat PCV2 diseases. We have previously reported that the synergistic anti-PCV2 effects of Matrine and Osthole were better than Matrine or Osthole alone in vitro, Matrine and Osthole were purchased with a clear content, chemical structure and plant origin. This study aimes to evaluate theirs synergistic anti-PCV2 effect and mechanism in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups, namly: normal control group, PCV2 infected group, Matrine combined with Osthole high dose treatment group (40 mg/kg + 12 mg/kg), medium dose treatment group (20 mg/kg + 6 mg/kg), low dose treatment group (10 mg/kg + 3 mg/kg), Matrine treatment group (40 mg/kg), Osthole treatment group (12 mg/kg) and Ribavirin positive control group (40 mg/kg). PCV2 was intraperitoneally (i.p.) injected in all mice except the normal control group. At 5 days post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for 5 consecutive days. Results The synergistic inhibition effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly stronger than that of Matrine and Osthole alone. The protein expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax were significantly reduced, but the protein expression of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological change caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. Conclusions The synergistic effect of anti-apoptosis was better than that of Matrine and Osthole alone, although both of Matrine and Osthole could also directly inhibited the expression of PCV2 Cap and then inhibited the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provide a new insight into controlling PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

2018 ◽  
Vol 6 (2) ◽  
pp. 272
Author(s):  
Niki Niki Rahmawati ◽  
Sugiyanta Sugiyanta ◽  
Elly Nurus Sakinah

  High dose of paracetamol is metabolized by cytochrome P-450 become free radical N-acetyl-p-benzoquinoneimine (NAPQI) but liver Glutathione (GSH) is not adequate to change it become nonreactive metabolite so that NAPQI bind to unsaturated fatty acid of cell membrane, causing lipid peroxidation and increase liver Malondialdehyde (MDA). 'A' apple vinegar contains anthocyanin with an antioxidant effect by electron donor to NAPQI and acetic acid to improve liver GSH level. The aim of research was to investigate the effect of 'A' apple vinegar on the rat liver MDA induced by toxic dose of paracetamol. Research groups consist of normal control (CMC Na 1% 1 ml for 14 days), negative control (CMC Na 1% 1ml for 14 days + paracetamol 291.6 mg/200gBW on the day 12nd,13rd,14th), and treatment group ('A' apple vinegar 0.4 ml/150gBW for 14 days + paracetamol 291.6 mg/200gBW on the day 12nd,13rd,14th). Liver MDA was measured on the day 15th with competitive ELISA. The average of normal control group was 21.58 ng/ml, negative control group was 70,71 ng/ml, treatment group was 37,67 ng/ml. One way ANOVA and Post hoc LSD test showed significantly differences between all groups (p<0,05). It can be concluded that 'A' apple vinegar had an effect on the liver MDA induced by toxic dose of paracetamol.   Keywords: Paracetamol, NAPQI, MDA, 'A' apple vinegar, antioxidant  


2020 ◽  
Author(s):  
Kun Wang ◽  
Huaping Du ◽  
Zhen Chen ◽  
Dong Xue

Abstract Background: In the present study, we aimed to assess whether adrenocorticotropic hormone (ACTH) could protect the podocytes from adriamycin (ADR)-induced injury by stimulating B lymphocytes to secrete the associated cytokines.Methods: The supernatant of B lymphocytes was respectively collected after B lymphocytes were intervened by phorbol myristate acetate (PMA) or ACTH4-10 (1 µg/L, 10 µg/L and 100 µg/L). Podocytes were randomly divided into the groups as follows: normal control group, adriamycin (ADR) group, the supernatant (1 µg/L, 10 µg/L, or 100 µg/L ACTH4-10)+ADR groups, ACTH4-10 (10 µg/L)+ADR group, and the supernatant (10 µg/L ACTH4-10)+anti-IL-10R+ADR group. Proliferation assay was used to assess the proliferation and activity of podocytes. Enzyme-linked immunosorbent assay was used to examine the secretion of IL-10 and IL-4. TUNEL apoptosis detection kit was used to detect podocyte apoptosis.Real-time PCR and western blotting were used to examine the mRNA and protein expression of nephrin and podocin.Results: Compared with the normal control group, the podocyte proliferation of ADR group was significantly inhibited. However, compared with the ADR group, the podocyte proliferation of the supernatant (1 µg/L, 10 µg/L or 100 µg/L ACTH4-10)+ADR groups was generally increased, and the proliferation effect of the supernatant containing 10 µg/L ACTH4-10 was the highest. Moreover, we found that after B lymphocytes were intervened by 10 µg/L ACTH4-10, the IL-10 level in the cell supernatant was significantly elevated (p <0.05). When anti-IL-10R was added, the podocyte proliferation of the supernatant (10 µg/L ACTH4-10)+ADR group was significantly inhibited. Furthermore, the supernatant of B cells stimulated with 10 µg/L ACTH4-10 could better decrease the apotosis rate of injuried podocytes and increase the mRNA and protein expression of nephrin and podocin by elevating the secretion of IL-10.Conclusions: Compared with ACTH4-10, the supernatant of B cells stimulated with ACTH4-10 could better protect the podocytes from ADR-induced injury by elevating the secretion of IL-10.


2021 ◽  
Vol 18 (7) ◽  
pp. 1449-1454
Author(s):  
Jian Huang ◽  
Dan Wang ◽  
Anye Zhang ◽  
Qinglian Zhong ◽  
Qun Huang

Purpose: To investigate the protective effect and mechanism of action of Lactobacillus rhamnosus against colorectal cancer (CRC). Methods: A total of 40 healthy female Sprague Dawley rats weighing 100 – 140 g (mean weight = 120 ± 20 g) were used for this study. The rats were randomly assigned to four groups of 10 rats each: normal control group, L. rhamnosus group; 1, 2-dimethylhydrazine (DMH) group and treatment group. Rats in L. rhamnosus group were inoculated with L. rhamnosus (1 x 108 CFU/mL) orally for 20 weeks, while rats in DMH group received 35 mg DMH/kg /week intraperitoneally for 10 weeks for induction of CRC. Treatment group rats received 35 mg DMH/kg bwt intraperitoneally for 10 weeks for induction of CRC, and were treated with L. rhamnosus (1 x 108 CFU/mL) orally for 20 weeks. After 20 weeks, the rats were euthanized using ether anesthesia. Expressions of inflammatory, angiogenesis and proapoptotic genes were determined using Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Treatment with L. rhamnosus significantly reduced the incidence of CRC in the rats (p < 0.05). The incidence of multiple tumors in the treatment group was also significantly reduced, when compared to DMH group (p < 0.05). The protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), cyclooxygenase-2 (COX-2), bcl-2 and vascular endothelial growth factor α (VEGF-α) were significantly upregulated in DMH group, when compared with normal control group (p < 0.05). However, treatment with L. rhamnosus significantly down-regulated the expressions of these proteins (p < 0.05). DMH treatment also significantly upregulated the expressions of iNOS, TNF-α, VEGF-α, NF-kB, β-catenin and bax genes (p < 0.05). However, L. rhamnosus significantly reversed the effects of DMH on the expression levels of these genes (p < 0.05). Conclusion: These results show that L. rhamnosus prevents CRC via suppression of expressions of inflammatory and angiogenesis genes, and upregulation of apoptotic gene expression.


2020 ◽  
Vol 24 (8) ◽  
pp. 1335-1340
Author(s):  
M. Dikko ◽  
Y. Sarkingobir

The objective of this study was to investigate histopathology of livers and carry out body weight determination in normal rats administered with  tamsulosin. Standard methods and procedures were used in this study. The results were revealed. Pertaining weight, at the 3rd , 6th and 8th weeks of the study, no significant difference (P>0.05) in weight was found in the group of rats treated with carvedilol (positive control), tamsulosin low dose (12μg/kg) and high dose tamsulosin (40μg/kg) compared to normal control group, respectively. Other inter-groups comparisons were not significantly different, respectively. Pertaining liver morphology, liver sections of groups revealed no significant histological lesions compared to the normal control group at the 6th and 8th weeks of the study, respectively. This study revealed that the tamsulosin cause no histopathological lesion, thus the drug might be safe to the liver and its biochemical processes. Keywords: Tamsulosin, Liver, histopathology, weight, Wistar rats


2021 ◽  
Vol 14 (1) ◽  
pp. 31-37
Author(s):  
N.S. Sadi ◽  
S.M. Abubakar ◽  
A. Ibrahim ◽  
A.M. Umar ◽  
A.M. Gadanya ◽  
...  

Tamarind tree is a multipurpose tree of which almost every part finds at least some use, either nutritional or medicinal. Due to its pleasant acidic taste and rich aroma, the pulp is widely used for domestic and industrial purpose. A study was carried out to evaluate the effect of Tamarind juice intake in CCl4 induced oxidative stress albino rats. The Proximate, antinutrient, and Phytochemical contents of tamarind juice were analyzed using standard AOAC methods while mineral contents were determined using atomic absorption spectrometry. Oxidative stress markers were also analyzed using colorimetric assay kit. The serum levels of oxidative stress markers were compared between the normal and test groups. Experimental rats were divided into five groups: Normal control group, negative control (CCl4) group, standard drug (Vitamin C) group, tamarind low and high dose group. At the end of the experiment, significant increase in malondialdehyde level and decrease in superoxide dismutase, catalase, reduced glutathione and glutathione Peroxidase activities were recorded in CCl4-exposed rats as compared to normal control group. In the tamarind supplemented groups, the level of MDA along with the activities of SOD, CAT, GSH and GPx were comparable with the normal control rats (p>0.05). Thus, it appears that tamarind juice ameliorate the effect of CCl4; suggesting that consumption of natural compounds with an antioxidant profile may be a preventive alternative to those diseases associated with oxidative stress.


Author(s):  
F. C. Anacletus ◽  
B. Nwakaku ◽  
K. T. Nwauche

The antioxidant protective effects of fruit juice of cucumber and watermelon on lipid profile of cadmium induced toxicity on male albino rats was investigated. Forty male rats were divided into eight groups. Group NC served as normal control group while group PC was positive control that was not treated but induced with cadmium. Groups I to VI received high dose and low dose of juice of Cucumber and Watermelon respectively. Excluding the normal control group, other groups were fed with lard 14 days before treatment commenced.  Doses of 0.8 mg/kg-high dose and 0.4 mg/kg-low dose for cucumber and watermelon respectively. At the 4th and 6th week, biochemical parameters were assayed. Results revealed that the levels of total cholesterol, LDL, VLDL and triglyceride significantly (P˂0.05) were decreased compared to positive control but HDL was increased in treatment groups compared to positive control. Pretreatment with cucumber and watermelon juice indicated that total cholesterol, LDL, VLDL and triglyceride significantly (P˂0.05) were decreased compared to positive control but HDL was increased in treatment groups compared to positive control. The result also revealed an increase in testosterone levels in treated groups after 4 weeks of administration of whole extract of cucumber and watermelon when compared to their week 2 values. Testosterone level in positive control was also reduced significantly from 1.5±0.14 ng/ml to 0.46±0.31 ng/ml. Histological evaluation of the testes of normal control group revealed that the interstitium was intact with leydig cells present and maturing germ cells embedded in normal seminiferous tubules while the other groups that were induced with cadmium only showed morphology of testes with empty seminiferous tubules and consolidated interstitial spaces.


Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.


Author(s):  
Xitong Yang ◽  
Pengyu Wang ◽  
Shanquan Yan ◽  
Guangming Wang

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.


2014 ◽  
Vol 1033-1034 ◽  
pp. 220-223
Author(s):  
Xue Mei Han ◽  
Li Bo Wang ◽  
Ni Ni Li ◽  
Song Yan Liu

To examine the effect of GDM on the expression of MT1-MMP and u-PA genes in glioma cells. Glioma cell lines U251 and U87 were cultured in DMEM medium supplemented with 10% fetal bovine serum. RT-PCR was used to identify gene expression level. The level of u-PA mRNA was up-regulated significantly in the HGF group compared with the normal control group (P<0.05). The expression of MT1-MMP and u-PA was significantly lower in the GDM group than in the normal control and HGF groups (P<0.05). The expression of u-PA in the HGF+GDM group was down-regulated significantly compared with the normal control and HGF groups (P<0.05).GDM can inhibit expression of both MT1-MMP and u-PA in glioma cells.


2021 ◽  
Author(s):  
Jinglei Li ◽  
Wei Hou

Abstract Purpose: Lung adenocarcinoma (LUAD) has high heterogeneity and poor prognosis, posing a major challenge to human health worldwide. Therefore, it is necessary to improve our understanding of the molecular mechanism of LUAD in order to be able to better predict its prognosis and develop new therapeutic strategies for target genes.Methods: The Cancer Genome Atlas and Gene Expression Omnibus, were selected to comprehensively analyze and explore the differences between LUAD tumors and adjacent normal tissues. Critical gene information was obtained through weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and survival analysis.Results: Using WGCNA and differential gene expression analysis, 29 differentially expressed genes were screened. The functional annotation analysis showed these genes to be mainly concentrated in heart trabecula formation, regulation of inflammatory response, collagen-containing extracellular matrix, and metalloendopeptidase inhibitor activity. Also, in the protein–protein interaction network analysis, 10 central genes were identified using Cytoscape's CytoHubba plug-in. The expression of CDH5, TEK, TIMP3, EDNRB, EPAS1, MYL9, SPARCL1, KLF4, and TGFBR3 in LUAD tissue was found to be lower than that in the normal control group, while the expression of MMP1 in LUAD tissue was higher than that in the normal control group. According to survival analysis, the low expression of MYL9 and SPARCL1 was correlated with poor overall survival in patients with LUAD. Finally, through the verification of the Oncomine database, it was found that the expression levels of MYL9 and SPARCL1 were consistent with the mRNA levels in LUAD samples, and both were downregulated.Conclusion: Two survival-related genes, MYL9 and SPARCL1, were determined to be highly correlated with the development of LUAD. Both may play an essential role in the development LUAD and may be potential biomarkers for its diagnosis and treatment in the future.


Sign in / Sign up

Export Citation Format

Share Document