{"title":"Piceatannol promotes hepatic and renal AMPK/SIRT1/PGC-1α mitochondrial pathway in rats exposed to reserpine or gamma-radiation.","authors":"Enas Mahmoud Moustafa, Engy Refaat Rashed, Rasha Refaat Rashed, Nesreen Nabil Omar","doi":"10.1177/20587384211016194","DOIUrl":"10.1177/20587384211016194","url":null,"abstract":"<p><p>Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients' quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of \"mitochondrial biogenesis\" signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins' tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211016194"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/30/10.1177_20587384211016194.PMC8127740.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38909147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic effects of SKF-96365 on murine allergic rhinitis induced by OVA.","authors":"Guangyi Ba, Ru Tang, Xiwen Sun, Zhipeng Li, Hai Lin, Weitian Zhang","doi":"10.1177/20587384211015054","DOIUrl":"10.1177/20587384211015054","url":null,"abstract":"<p><strong>Introduction: </strong>SKF-96365 is regarded as an inhibitor of receptor-mediated calcium ion (Ca<sup>2+</sup>) entry. The current study aimed to explore the effects of SKF-96365 on murine allergic rhinitis (AR).</p><p><strong>Methods: </strong>Intranasal SKF-96365 administration was performed on OVA induced murine AR. Serum and nasal lavage fluid (NLF) from mice were harvested to assay IgE and inflammatory cytokines using ELISA method. Inflammatory cells were counted and analyzed in NLF. Nasal mucosa tissues were collected from mice and used for HE staining, immunohistochemistry (IHC) staining, and real-time PCR detection.</p><p><strong>Results: </strong>SKF-96365 had therapeutic effects on murine AR manifesting attenuation of sneezing, nasal rubbing, IgE, inflammatory cytokines, inflammatory cells, TRPC6 immunolabeling, and TRPC6, STIM1 and Orai1 mRNA levels in AR mice.</p><p><strong>Conclusion: </strong>SKF-96365 could effectively alleviate the symptoms of murine AR. SKF-96365 could suppress TRPC6, STIM1, and Orai1 activities, leading to the downregulation of inflammatory cytokines and inflammatory cells in murine AR.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211015054"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/ca/10.1177_20587384211015054.PMC8127738.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38988529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jihua Tian, Sijia Chang, He Ji, Taiping Huang, Haixiu Guo, Jing Kang, Yanhong Wang, Yun Zhou
{"title":"The p70S6K/PI3K/MAPK feedback loop releases the inhibition effect of high-dose rapamycin on rat mesangial cell proliferation.","authors":"Jihua Tian, Sijia Chang, He Ji, Taiping Huang, Haixiu Guo, Jing Kang, Yanhong Wang, Yun Zhou","doi":"10.1177/20587384211000544","DOIUrl":"https://doi.org/10.1177/20587384211000544","url":null,"abstract":"<p><p>Glomerular mesangial cell (MC) proliferation is one of the causative factors of glomerular diseases and one of their prominent pathological features. Rapamycin can inhibit MC proliferation and slow the progression to chronic renal fibrosis. The present study was designed to observe the role of rapamycin in MC proliferation and to explore the mechanism by which rapamycin acts on Akt and MAPK/ERK1/2 pathways in mesangial cells. MTT assay and flow cytometry were used to evaluate the proliferation and the cell cycle phase of glomerular mesangial cells respectively. The mRNA expression level of p70S6K was detected by RT-qPCR. Western blotting was performed to determine p70S6K, PI3K/Akt, and PI3K/MAPK protein expression. We found that rapamycin could reduce mesangial cell proliferation and arrest the cell cycle in the G1 phase, however the inhibition effect of 1000 nmol/L rapamycin was not higher than that in the 100 nmol/L group. The results of western blotting showed that 1000 nmol/L rapamycin more significantly inhibited the phosphorylation of p70S6K than 100 nmol/L, suggesting there should be another signaling pathway that activates the proliferation of MCs. Moreover, our results revealed that 1000 nmol/L rapamycin led to Raf1-MEK1/2-ERK pathway activation through a p70S6K-PI3K-mediated feedback loop in MCs. This study demonstrated that high-dose rapamycin leads to ERK1/2 activation through a p70S6K/PI3K/MAPK feedback loop in rat MCs, thus reducing the inhibitory effect of rapamycin on MC proliferation.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211000544"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/20587384211000544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39031222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dedifferentiated liposarcoma with abrupt transition of low-grade and high-grade dedifferentiation: A rare case report.","authors":"Yang Wen, Xianglei He, Ming Zhao","doi":"10.1177/20587384211048565","DOIUrl":"https://doi.org/10.1177/20587384211048565","url":null,"abstract":"<p><p>Dedifferentiated liposarcoma is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211048565"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/64/10.1177_20587384211048565.PMC8504230.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39497074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hager S Taha, Enas M Moustafa, Fatma Sm Moawed, Marwa Ga Hegazy
{"title":"Curative role of mesenchymal stromal cells in chronic pancreatitis: Modulation of MAPK and TGF-β1/SMAD factors.","authors":"Hager S Taha, Enas M Moustafa, Fatma Sm Moawed, Marwa Ga Hegazy","doi":"10.1177/20587384211054036","DOIUrl":"10.1177/20587384211054036","url":null,"abstract":"<p><strong>Background and objective: </strong>Living organisms respond to physical, chemical, and biological threats with a potent inflammatory response which alters organ cell signaling and leads to dysfunction. We evaluated the therapeutic effect of bone marrow-based mesenchymal stromal cell (BM-MSC) transplanted in rats to preserve tissue integrity and to restore homeostasis and function in the pancreatitis experimental pattern.</p><p><strong>Methods: </strong>This study involved 40 adult male Wister rats. Repeated L-arginine injections caused chronic pancreatitis (CP), leading to the development of pancreatic damage and shifting the intracellular signaling pathways. Rats were then infused with BM-MSC labeled with PKH26 fluorescent linker dye for 12 weeks.</p><p><strong>Results: </strong>Cell-surface indicators of BM-MSCs such as CD 90 and CD29 were expressed with the lack of CD34 expression. BM-MSC treatment considerably improved the alterations induced in a series of inflammatory markers, including IL-18, TNF-α, CRP, PGE2, and MCP-1. Furthermore, improvement was found in digestive enzymes and lipid profile with amelioration in myeloperoxidase activity. BM-MSC treatment also regulated the (TGF-/p-38MPAK/SMAD2/3) signaling factors that enhances repair of damaged pancreatic tissue, confirmed by reversed alteration of histopathological examination.</p><p><strong>Conclusion: </strong>our results further bring to light the promise of cell transplant therapy for chronic pancreatitis.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211054036"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/ed/10.1177_20587384211054036.PMC8552371.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39557341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural killer cell deficiency experiences higher risk of sepsis after critical intracerebral hemorrhage.","authors":"Yu Feng, Qian Wu, Tingbao Zhang, Jincao Chen, Xiaohui Wu","doi":"10.1177/20587384211056495","DOIUrl":"https://doi.org/10.1177/20587384211056495","url":null,"abstract":"<p><strong>Background: </strong>Lymphopenia is common in intracerebral hemorrhage (ICH) and may predispose to severe infections such as sepsis. However, what specific kind of lymphocytes subsets decreases is still unclear. We investigated the impact of lymphocytes subsets on post-critical ICH infections and mortality.</p><p><strong>Methods: </strong>Consecutive ICH patients (admitted to a single center between January 2017 and January 2018) were prospectively assessed to evaluate the following main parameters: peripheral blood lymphocytes, infections, and clinical scores. Predicting factors of sepsis were measured using multivariate Logistic regressions analysis. A Kaplan-Meier survival curve was performed to compare the mortality between septic and nonseptic patients. Survival status was evaluated by multivariate Cox regression analysis.</p><p><strong>Results: </strong>In total, 112 critical ICH cases were enrolled including 29 septic patients. Total counts of lymphocytes decreased accordingly with reduced lymphocyte subsets, especially natural killer (NK) cells and CD8<sup>+</sup>T lymphocytes after ICH. Septic patients had a higher incidence of pneumonia, a longer length of stay, higher 90-day mortality, and worse long-term outcomes. Multivariate Logistic regression analysis showed venous catheterization, high APACHE-II score (>15), low GCS score (3-5), and NK cells percentages on admission were independently associated with ensuing sepsis. After sepsis, the percentages of CD4+T and NK cells percentages decreased, CD8+T cells increased followed by a significantly decreased CD4/CD8 ratio. Bloodstream infection alone directly affected the survival status of patients with sepsis.</p><p><strong>Conclusions: </strong>Critical ICH patients underwent immune dysfunction and NK cells deficiency could favor nosocomial threatening sepsis after ICH.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211056495"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/a6/10.1177_20587384211056495.PMC8725218.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39620962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of the sphingosine axis in immune regulation: A dichotomy in the anti-inflammatory effects between sphingosine kinase 1 and sphingosine kinase 2-dependent pathways.","authors":"Yuval Ishay, Dvorah Rotnemer-Golinkin, Yaron Ilan","doi":"10.1177/20587384211053274","DOIUrl":"10.1177/20587384211053274","url":null,"abstract":"<p><p><i>Background:</i> Sphingosine kinase has been identified as playing a central role in the immune cascade, being a common mediator in the cellular response to a variety of signals. The different effects of sphingosine kinase 1 and 2 (SphK1 and SphK2, respectively) activity have not been completely characterized. <i>Aim:</i> To determine the different roles played by SphK1 and SphK2 in the regulation of immune-mediated disorders. <i>Methods:</i> Nine groups of mice were studied. Concanavalin A (ConA) injection was used to induce immune-mediated hepatitis. Mice were treated with SphK1 inhibitor (termed SphK-I) and SphK2 inhibitor (termed ABC294640), prior to ConA injection, and effects of treatment on liver enzymes, subsets of T lymphocytes, and serum levels of cytokines were observed. <i>Results:</i> While liver enzyme elevation was ameliorated by administration of SphK1 inhibitor, SphK2 inhibitor-treated mice did not show this tendency. A marked decrease in expression of CD25<sup>+</sup> T-cells and Foxp+ T-cells was observed in mice treated with a high dose of SphK1 inhibitor. Alleviation of liver damage was associated with a statistically significant reduction of serum IFNγ levels in mice treated with SphK1 inhibitor and not in those treated with SphK2 inhibitor. <i>Conclusions:</i> Early administration of SphK1 inhibitor in a murine model of immune-mediated hepatitis alleviated liver damage and inflammation with a statistically significant reduction in IFN-γ levels. The data support a dichotomy in the anti-inflammatory effects of SphK1 and SphK2, and suggests that isoenzyme-directed therapies can improve the effect of targeting these pathways.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211053274"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/28/10.1177_20587384211053274.PMC8645305.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39632343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lobna M Anees, Gehan R Abdel-Hamid, Ahmed A Elkady
{"title":"A nano based approach to alleviate cisplatin induced nephrotoxicity.","authors":"Lobna M Anees, Gehan R Abdel-Hamid, Ahmed A Elkady","doi":"10.1177/20587384211066441","DOIUrl":"10.1177/20587384211066441","url":null,"abstract":"<p><strong>Background and objective: </strong>Cisplatin, an effective drug against cancer, commonly induces nephrotoxicity; limiting its therapeutic efficacy and application. In this study, Cisplatin NanoComposite (Cis NC) was formulated successfully from irradiated chitosan coated Cisplatin and MgO nanoparticles (CHIT/Cis/MgO NPs) to promote cisplatin release in a more sustained manner to improve therapeutic efficacy via the reduction of its nephrotoxicity. To compare the relative induced renal toxicity of cisplatin with Cisplatin NanoComposite, histological and biochemical mechanisms underlying nephrotoxicity were investigated.</p><p><strong>Methods: </strong>Thirty rats were equally separated to three groups, first group received saline injections and adjusted as the control group, the second group was injected intra-peritoneal with cisplatin 0.64 mg/kg b. wt./day for 6 weeks, the third group was injected intra-peritoneal with Cis NC 5.75 mg/kg b. wt. daily for 6 weeks.</p><p><strong>Results: </strong>Cisplatin-induced renal functional impairment and histopathological damages in the kidney; also, cisplatin disrupted the balance of the redox system in renal tissue, stimulated the inflammatory reactions in the kidney via triggering signal transducer and activator of transcription-1 (STAT1) dependent pathways. Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. On the other hand, Cis NC exerted a minimal stimulatory effect on apoptotic and inflammatory signal cascade with negligible renal functional and morphological alterations.</p><p><strong>Conclusion: </strong>We postulated that Cis NC may be a valued possible drug to decrease the cytotoxicity of cisplatin thus reserves the renal function and structure.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211066441"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/93/10.1177_20587384211066441.PMC8725228.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39732787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Na Huang, Rui Zhou, Haiyan Chen, Shu Zhang, Jun Li, Wei Wei, Jin Sun, Song Ren, Baohua Li, Hong Deng, Jun Yang, Fanpu Ji, Zongfang Li
{"title":"Splenic CD4<sup>+</sup> and CD8<sup>+</sup> T-cells highly expressed PD-1 and Tim-3 in cirrhotic patients with HCV infection and portal hypertension.","authors":"Na Huang, Rui Zhou, Haiyan Chen, Shu Zhang, Jun Li, Wei Wei, Jin Sun, Song Ren, Baohua Li, Hong Deng, Jun Yang, Fanpu Ji, Zongfang Li","doi":"10.1177/20587384211061051","DOIUrl":"https://doi.org/10.1177/20587384211061051","url":null,"abstract":"<p><p><b>Introduction:</b> The spleen plays an important role in regulating the immune response to infectious pathogens. T-cells dysfunction and exhaustion have been reported in patients with hepatitis B/C virus (HBV/HCV) infection, which contributes to persistent virus infection. The aims of this study were to investigate spleen-related evidence of immunosuppression and immune tolerance in HCV cirrhotic patients with portal hypertension (PH). <b>Methods:</b> The expression of programmed cell death 1 (PD-1), T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) and its ligand PD-L1/2, and Galectin-9 in the spleens and livers of HCV cirrhotic patients (<i>n</i> = 15) was analyzed using real-time PCR and immunohistochemistry. Flow cytometry was used to evaluate the expression of PD-1 and Tim-3 on splenic T-cells and the peripheral blood T-cells before and after splenectomy (<i>n</i> = 8). <b>Results:</b> Spleens from patients with PH showed significantly increased mRNA levels of PD-L2, Tim-3, Galectin-9, CD80, and CD86, and decreased levels of CD28 compared to control spleens (spleens removed due to traumatic injury) (all <i>p</i> < 0.05). Additionally, protein expression of inhibitory signaling molecules was significantly increased in both the spleens and livers of cirrhotic patients compared with controls (all <i>p</i> < 0.05). Peripheral blood and splenic CD4<sup>+</sup> and CD8<sup>+</sup> T-cells also expressed higher protein levels of PD-1, Tim-3, and CTLA-4 in cirrhotic patients as compared with healthy controls (all <i>p</i> < 0.05). The proportion of PD-1<sup>+</sup>CD4<sup>+</sup>T lymphocytes (26.2% ± 7.12% vs. 21.0% ± 9.14%, <i>p</i> = 0.0293) and Tim-3<sup>+</sup>CD8<sup>+</sup> T lymphocytes (9.4% ± 3.04% vs. 6.0% ± 2.24%, <i>p</i> = 0.0175) in peripheral blood decreased followed splenectomy. <b>Conclusion:</b> The CD4<sup>+</sup> and CD8<sup>+</sup> T-cells in spleen and peripheral blood highly expressed PD-1 and Tim-3 in HCV-infected and cirrhotic patients with portal hypertension. Highly expressed PD-1 and Tim-3 in peripheral blood T-lymphocytes can be partly reversed following splenectomy.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211061051"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/9f/10.1177_20587384211061051.PMC8725229.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39742756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liquiritigenin enhances cyclic adenosine monophosphate production to mitigate inflammation in dendritic cells.","authors":"Mingming Qin, Aili Guo, Feng Li, Fuxiang Zhang, Meirong Bi, Yamin Zhang, Weiwei Zhu","doi":"10.1177/20587384211038098","DOIUrl":"https://doi.org/10.1177/20587384211038098","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to dissect the mechanism of traditional Chinese medicinal herbs against asthma; we chose to first focus on the main chemical components of licorice to investigate their contribution to asthmatic inflammation inhibition.</p><p><strong>Methods: </strong>Production of cellular nucleotide molecules such as cAMP, cGMP, and cGAMP was examined by using enzyme-linked immunosorbent assay (ELISA). Enzyme-encoding genes were tested <i>in vitro</i> using quantitative real-time PCR and protein level was detected by Western blotting analysis. In addition, co-culturing of murine dendritic cells together with T cells was conducted to examine the expression of cytokine genes and host immune response.</p><p><strong>Results: </strong>We found that one of the components within licorice, named liquiritigenin (LR), could efficiently enhance cAMP production in different cell lines. The augmentation of such molecules was linked to the high expression of cAMP synthesis genes and repressed expression of cAMP breaking down genes. In addition, the downstream immune response was also alleviated by the increase in cAMP levels by LR, suggesting the great potential of this molecule against inflammation. Subsequent immunological tests showed that LR could efficiently inhibit the expression of several cytokines and alter the NF-κB pathway and T cell polarization.</p><p><strong>Conclusion: </strong>Altogether, we have identified a promising antiasthmatic agent LR that could exhibit immunosuppressive function by elevating the cAMP level.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"35 ","pages":"20587384211038098"},"PeriodicalIF":3.5,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c7/d1/10.1177_20587384211038098.PMC8728780.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}