scholarly journals In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Huilong Fang ◽  
Ling Yu ◽  
Da You ◽  
Nan Peng ◽  
Wanbei Guo ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mrna Expression ◽  
Hepatic Fibrosis ◽  
Inflammatory Factors ◽  
Control Group ◽  
Therapeutic Effects ◽  
Type I ◽  
Expression Levels ◽  
Tnf Α ◽  
Mrna Expression Levels

Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis.Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis.Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α.Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone.Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.

Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li
Keyword(s):  
Plasma Concentration ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Control Group ◽  
Gene Expressions ◽  
Expression Levels ◽  
Tnf Α ◽  
Healthy Control ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

scholarly journals The influence on oxidative stress markers, inflammatory factors and intestinal injury-related molecules in Wahui pigeon induced by lipopolysaccharide

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251462
Author(s):  
Fei Wang ◽  
Jin Liu ◽  
Xiaofen Hu ◽  
Youbao Zhong ◽  
Feng Wen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Histopathological Examination ◽  
Intestinal Injury ◽  
Inflammatory Factors ◽  
Control Group ◽  
Inflammatory Factor ◽  
Expression Levels ◽  
Lps Challenge ◽  
Mrna Expression Levels

Introduction The intestinal structure is the foundation for various activities and functions in poultry. An important question concerns the changes in the intestinal status under endotoxin stimulation. This study aimed to investigate the mechanism of intestinal injury induced by lipopolysaccharide (LPS) in Wahui pigeons. Methods Thirty-six 28-day-old healthy Wahui pigeons were randomly divided into two groups. The experimental group was injected with LPS (100 μg/kg) once per day for five days, and the control group was treated with the same amount of sterile saline. Blood and the ileum were collected from pigeons on the first, third, and fifth days of the experiment and used for oxidative stress assessment, inflammatory factor detection, histopathological examination, and positive cell localization. In addition, intestinal injury indices and mRNA expression levels (tight junction proteins, inflammatory cytokines, and factors related to autophagy and apoptosis) were evaluated. Results Villi in the ileum were shorter in the LPS group than in the control group, and D-lactic acid levels in the serum were significantly increased. Glutathione and catalase levels significantly decreased, but the malondialdehyde content in the serum increased. TNF-α and IL-10 were detected at higher levels in the serum, with stronger positive signals and higher mRNA expression levels, in the LPS group than in the control group. In addition, the levels of TLR4, MyD88, NF-κB, and HMGB1 in the inflammatory signaling pathway were also upregulated. Finally, the mRNA expression of Claudin3, Occludin, and ZO-1 was significantly decreased; however, that of Beclin1 and Atg5 was increased in the LPS group. Conclusion Ileal pathological changes and oxidative stress were caused by LPS challenge; it is proposed that this triggering regulates the inflammatory response, causing excessive autophagy and apoptosis, promoting intestinal permeability, and leading to intestinal injury in Wahui pigeons.

scholarly journals Clinical Usefulness of Monitoring Expression Levels ofCCL24(Eotaxin-2) mRNA on the Ocular Surface in Patients with Vernal Keratoconjunctivitis and Atopic Keratoconjunctivitis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Yukiko Shiraki ◽  
Jun Shoji ◽  
Noriko Inada
Keyword(s):  
Mrna Expression ◽  
Ocular Surface ◽  
Clinical Score ◽  
Clinical Severity ◽  
Vernal Keratoconjunctivitis ◽  
Control Group ◽  
Expression Levels ◽  
Atopic Keratoconjunctivitis ◽  
Clinical Scores ◽  
Mrna Expression Levels

Purpose. This study aimed to evaluate the clinical efficacy of using expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface as a biomarker in patients with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).Methods. Eighteen patients with VKC or AKC (VKC/AKC group) and 12 control subjects (control group) were enrolled in this study. The VKC/AKC clinical score was determined by objective findings in patients by using the 5-5-5 exacerbation grading scale. All subjects underwent modified impression cytology and specimens were obtained from the upper tarsal conjunctiva. Expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface were determined using real-time reverse transcription polymerase chain reaction.Results. The VKC group was divided into two subgroups, depending on the clinical score: the active stage subgroup with 100 points or more of clinical scores and the stable stage subgroup with 100 points or less.CCL24(eotaxin-2) mRNA expression levels in the active VKC/AKC stage subgroup were significantly higher than those in the stable VKC/AKC subgroup and the control group. Clinical scores correlated significantly withCCL24(eotaxin-2) mRNA expression levels in the VKC group.Conclusions.CCL24(eotaxin-2) mRNA expression levels on the ocular surface are a useful biomarker for clinical severity of VKC/AKC.

Losartan attenuates paraquat-induced pulmonary fibrosis in rats

2014 ◽  
Vol 34 (5) ◽  
pp. 497-505 ◽  
Author(s):  
F Guo ◽  
YB Sun ◽  
L Su ◽  
S Li ◽  
ZF Liu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Mrna Expression ◽  
Collagen Type ◽  
Collagen Type I ◽  
Control Group ◽  
Type I ◽  
Expression Levels ◽  
Relative Expression ◽  
Tgf Β1

Paraquat (PQ) is one of the most widely used herbicides in the world and can cause pulmonary fibrosis in the cases with intoxication. Losartan, an angiotensin II type 1 receptor antagonist, has beneficial effects on the treatment of fibrosis. The aim of this study was to examine the effect of losartan on pulmonary fibrosis in PQ-intoxicated rats. Adult male Sprague Dawley rats ( n = 32, 180–220 g) were randomly assigned to four groups: (i) control group; (ii) PQ group; (iii) PQ + losartan 7d group; and (iv) PQ + losartan 14d group. Losartan treatment (intragastrically (i.g.), 10 mg/kg) was performed for 7 and 14 days after a single i.g. dose of 40 mg/kg PQ. All rats were killed on the 16th day, and hematoxylin–eosin and Masson’s trichrome staining were used to examine lung injury and fibrosis. The levels of hydroxyproline and transforming growth factor β1 (TGF-β1), matrix metallopeptidase 9 (Mmp9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) messenger RNA (mRNA) expression and relative expression levels of collagen type I and III were also detected. PQ caused a significant increase in hydroxyproline content, mRNA expression of TGF-β1, Mmp9, and TIMP-1, and relative expression levels of collagen type I and III (  p < 0.05), while losartan significantly decreased the amount of hydroxyproline and downregulated TGF-β1, Mmp9, and TIMP-1 mRNA and collagen type I and III expressions (  p < 0.05). Histological examination of PQ-treated rats showed lung injury and widespread inflammatory cell infiltration in the alveolar space and pulmonary fibrosis, while losartan could markedly reduce such damage and prevent pulmonary fibrosis. The results of this study indicated that losartan could reduce lung damage and prevent pulmonary fibrosis induced by PQ.

Cytokine Gene Expression and IgA Production in the Spleen of Chickens Infected with Eimeria tenella

2020 ◽  
Author(s):  
Liushu Jia ◽  
Bianhua Zhou ◽  
Hongwei Wang ◽  
Fan Yang ◽  
Guoyong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Morphological Characteristics ◽  
Eimeria Tenella ◽  
Cytokine Gene Expression ◽  
Control Group ◽  
Expression Levels ◽  
New Strategy ◽  
Iga Production ◽  
Mrna Expression Levels

To explore the effect of Eimeria tenella infection on the cytokines gene expression and IgA production in the spleen of chickens, the morphological characteristics of the spleen were observed through optical and transmission electron microscopy. The IgA production was determined through immunohistochemistry. The mRNA expression levels of splenic cytokines were detected through real-time PCR. Compared to the control group, along with the infection of E. tenella, the splenic lymphocytes exhibited irregular and cracked membranes, mitochondria swelled even vacuolization, the IgA expression in spleen tissue was decreased by 55.57% (p lessthan 0.01). Likewise, the mRNA expression levels of IL-2 and IL-1â decreased by 40% (plessthan 0.01) and 43% p lessthan 0.05), respectively. By contrast, the IL-6, IFN-g and IL-10 levels increased by 158% (p lessthan 0.01), 464% (p lessthan 0.05) and 379% p lessthan 0.01), respectively. These results indicated that the spleen implement an important function in the antagonism of E. tenella, which suggest a new strategy to control coccidiosis by improving the peripheral immunity of chickens.

Herpes simplex virus type I infection of mature dendritic cells leads to reduced LMP7-mRNA-expression levels

Immunobiology ◽  
2009 ◽  
Vol 214 (9-10) ◽  
pp. 861-867 ◽  
Author(s):  
Jutta Eisemann ◽  
Alexander T. Prechtel ◽  
Petra Mühl-Zürbes ◽  
Alexander Steinkasserer ◽  
Mirko Kummer
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mrna Expression ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Type I ◽  
Expression Levels ◽  
Simplex Virus ◽  
Mrna Expression Levels

scholarly journals Th2 cytokine bias induced by silver nanoparticles in peripheral blood mononuclear cells of common bottlenose dolphins (Tursiops truncatus)

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5432 ◽  
Author(s):  
Wen-Ta Li ◽  
Lei-Ya Wang ◽  
Hui-Wen Chang ◽  
Wei-Cheng Yang ◽  
Chieh Lo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Bottlenose Dolphins ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Expression Levels ◽  
Th2 Cytokine ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mrna Expression Levels

Background Silver nanoparticles (AgNPs) have been widely used in many commercial products due to their excellent antibacterial ability. The AgNPs are released into the environment, gradually accumulate in the ocean, and may affect animals at high trophic levels, such as cetaceans and humans, via the food chain. Hence, the negative health impacts caused by AgNPs in cetaceans are of concern. Cytokines play a major role in the modulation of immune system and can be classified into two types: Th1 and Th2. Th1/Th2 balance can be evaluated by the ratios of their polarizing cytokines (i.e., interferon [IFN]-γ/Interleukin [IL]-4), and animals with imbalanced Th1/Th2 response may become more susceptible to certain kinds of infection. Therefore, the present study evaluated the in vitro cytokine responses of cetacean peripheral blood mononuclear cells (cPBMCs) to 20 nm citrate-AgNPs (C-AgNP20) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Methods Blood samples were collected from six captive common bottlenose dolphins (Tursiops truncatus). The cPBMCs were isolated and utilized for evaluating the in vitro cytokine responses. The cytokines evaluated included IL-2, IL-4, IL-10, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. The geometric means of two housekeeping genes (HKGs), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β2-microglobulin (B2M), of each sample were determined and used to normalize the mRNA expression levels of target genes. Results The ratio of late apoptotic/necrotic cells of cPBMCs significantly increased with or without concanavalin A (ConA) stimulation after 24 h of 10 µg/ml C-AgNP20 treatment. At 4 h of culture, the mRNA expression level of IL-10 was significantly decreased with 1 µg/ml C-AgNP20 treatment. At 24 h of culture with 1 µg/ml C-AgNP20, the mRNA expression levels of all cytokines were significantly decreased, with the exceptions of IL-4 and IL-10. The IFN-γ/IL-4 ratio was significantly decreased at 24 h of culture with 1 µg/ml C-AgNP20 treatment, and the IL-12/IL-4 ratio was significantly decreased at 4 or 24 h of culture with 0.1 or 1 µg/ml C-AgNP20 treatment, respectively. Furthermore, the mRNA expression level of TNF-α was significantly decreased by 1 µg/ml C-AgNP20 after 24 h of culture. Discussion The present study demonstrated that the sublethal dose of C-AgNP20 (≤1 µg/ml) had an inhibitory effect on the cytokine mRNA expression levels of cPBMCs with the evidence of Th2 cytokine bias and significantly decreased the mRNA expression level of TNF-α. Th2 cytokine bias is associated with enhanced immunity against parasites but decreased immunity to intracellular microorganisms. TNF-α is a contributing factor for the inflammatory response against the infection of intracellular pathogens. In summary, our data indicate that C-AgNP20 suppresses the cellular immune response and thereby increases the susceptibility of cetaceans to infection by intracellular microorganisms.

scholarly journals Effect of Qizhu Granule on Liver Sinusoidal Endothelial Cells Capillarization in Carbon Tetrachloride-Induced Rats Fibrosis.

2020 ◽  
Author(s):  
Rong Zhang ◽  
Shao Neng Liu ◽  
Zheng Ji Ma ◽  
Yuan Jia Ding ◽  
Min Hui Liu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Mapk Signaling ◽  
Cell Phenotype ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Liver Sinusoidal Endothelial Cells ◽  
Expression Levels ◽  
Endothelial Cell Surface

Abstract Background: Qizhu granule, a traditional Chinese medicine, has been widely used in clinic as a complementary and alternative medicine to treat liver fibrosis.However, the mechanism underlying its anti-hepatic fibrosis is still not clear. Liver fibrosis accompanied by liver sinusoidal pathological angiogenesis has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. In this study, we investigated the mechanism of anti-capillarization of this herbal drug against liver fibrosis.Materials and methods: The liver fibrosis rats model induced by 4-week of intervention with 40% CCl4 was employed in this study. Meanwhile, low, medium and high dose serum containing Qizhu granules were prepared. Liver tissues were acquired, and liver samples were subjected to histological studies.LSECs were isolated from liver fibrosis rats and were routinely cultured for 48h in low, medium and high dose of Qizhu granules-containing serum. The fenestration of LSECs in liver fibrosis rats were observed under scanning electron microscopy. The expression of the endothelial cell surface markers CD31, SE-1 and LSECs integrin ɑVβ3, FAK, p-FAK, Ras, MAPK, p-MAPK were measured by western blot.Results: Compared with the control group, the loss of fenestration of LSECs in the model group increased. After intervention of Qizhu granule-containing serum, the fenestration of the structure of LSECs in liver fibrosis induced by CCl4 increased, especially in the high-dose Qizhu granules group. ompared with the control group, the expression levels of SE-1 and CD31 in LSECs in the model group were significantly increased (P < 0.05). Compared with the model group, the expression levels of SE-1 and CD31 in LSECs of rats with hepatic fibrosis induced by CCl4 decreased after the treatment of low, medium and high dose serum containing Qizhu granules (P < 0.05). Among them, the expression levels of SE-1 and CD31 in LSECs of Qizhu granules group decreased with the increase of dosage, showing a dose-dependent relationship to a certain extent. Compared with the normal control group, the expression of integrin ɑVβ3, Ras, p-FAK and p-MAPK protein increased in the LSECs of model group(P <0.05). After treatment with Qizhu granule-containing serum, the expression of integrin ɑVβ3, p-FAK and p-MAPK protein in LSECs of liver fibrosis rats induced by CCl4 were reduced (P <0.05), and the expression of FAK, Ras and MAPK protein decreased ( P> 0.05).Conclusions: Qizhu granule could reduce the loss of fenestration of LSECs, transforming the cell phenotype of LSECs, and ameliorating the pathological remodeling of hepatic sinus capillarization in hepatic fibrosis induced by CCl4 in rats. It was found that Qizhu granules played an anti-fibrosis role by suppressing the expression of integrin ɑVβ3-FAK-Ras/MAPK signaling pathway of LSECs in CCl4-induced fibrosis rats.

scholarly journals Effect of Short-Term Endurance Exercise on COX IV and PGC-1a mRNA Expression Levels in Rat Skeletal Muscle

2019 ◽  
Vol 12 (3) ◽  
pp. 1309-1316 ◽  
Author(s):  
Nova Sylviana ◽  
Christina Natalia ◽  
Hanna Goenawan ◽  
Yuni Susanti Pratiwi ◽  
Iwan Setiawan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Control Group ◽  
Muscle Adaptation ◽  
Rat Skeletal Muscle ◽  
Short Term ◽  
Expression Levels ◽  
Mrna Expression Levels

Endurance exercise induces specific skeletal muscle adaptation by increasing mitochondrial oxidative phosphorylation eficiency and mitochondrial biogenesis. Many previous studies suggesting both PGC-1a and COX IV as a potential biomarker of skeletal muscle adaptation induced by exercise. But most of them only studied the effect of long-term endurance exercise, whereas the effect of short-term exercise remains unclear. To investigate short-term physiological adaptation induced by endurance exercise on expression of COX IV and PGC-1a mRNA in rat skeletal muscle. Twenty healthy male Wistar rats (Rattus norvegicus) aged 10-11 weeks old were used in this experiment. Rats were randomly assigned into 4 groups based on the time period of exercise: 1) control (C; n=5), 2) three days of exercise (E3; n=5), 3) six days of exercise (E6; n=5), 4) fifteen days of exercise (E15; n=5). The exercise groups were run at 20m/s for 30 minutes on the rat treadmill and the stationary control group was only placed inside treadmill with the machines turned off. On the last day of exercise, the rats were sacrificed then RNA from skeletal muscle was extracted. COX IV and PGC-1a mRNA expressions were measured by Reverse Transcriptase PCR. The results showed that there were statistically significant differences of PGC-1a mRNA expression levels in both soleus (F(3,16)=3.740, ps=0.033) and gastrocnemius (F(3,16)=3.969, pg=0.027) muscles. The COX IV mRNA expression levels in soleus (F(3,16)=3.801, ps=0.031) and gastrocnemius (F(3,16)=5.429, ps=0.009) muscles were also significantly increased. There were significant increases of PGC-1a and COX IV expressions in fifteen days of exercise group compared to control group in both muscles. Short-term endurance exercise induced mitochondrial biogenesis marker and mitochondrial activity marker by increasing the PGC-1a and COX IV mRNA expression levels in rat skeletal muscle significantly following the time periods of exercise.

Sign in / Sign up

Export Citation Format

Share Document