scholarly journals Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Stem Cell ◽  
Inflammatory Response ◽  
Murine Model ◽  
Licorice Root ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Stem Cell Markers ◽  
Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

Tumor Necrosis Factor, α-Induced Protein 3 Interacting Protein 2 is Involved in the Inflammatory Response in Sepsis via Inhibiting the Nuclear Factor-κB Pathway Activation

2020 ◽  
Vol 10 (4) ◽  
pp. 582-588
Author(s):  
Jia Li ◽  
Ye He ◽  
Yuping Li
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Nuclear Factor ◽  
Interacting Protein ◽  
Raw264.7 Macrophages ◽  
Pathway Activation ◽  
Tnf Α ◽  
Necrosis Factor

The study aimed to explore the role of TNFAIP3 interacting protein 2 (TNIP2) in lipopolysaccharide (LPS) induced RAW264.7 macrophages or septic mice. TNIP2 level was detected using quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. LPS-stimulated RAW264.7 macrophages were used to investigate the effects of TNIP2 on sepsis in vitro. In addition, septic mice model was established to validate the regulation of TNIP2 during inflammation response in vivo. The levels of inflammatory cytokines were assessed by enzyme-linked immunosorbent assay (ELISA). The data indicated that TNIP2 mRNA was down-regulated in the peripheral blood from sepsis patients. Interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α levels were significantly increased and the level of TNIP2 was suppressed in LPS-stimulated macrophages compared to the control group. TNIP2-plasmid promoted the TNIP2 expression in RAW 264.7 macrophages and reversed the effects of LPS on inflammatory factors and Nuclear factor-κ B (NFκ- B) pathway. The results also showed that TNIP2-plasmid alleviated inflammatory responses in septic mice, evidenced by the reduction in the levels of TNF-α , IL-1β and IL-6. TNIP2-plasmid also reduced the secretion of organ damage markers in septic mice serum. Our data indicated that TNIP2 was involved in the inflammatory response in sepsis via inhibiting the NF-κ B pathway activation.

Expression and Significance of Th17 Cells and Related Factors in Patients with Autoimmune Hepatitis

2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An
Keyword(s):  
Autoimmune Hepatitis ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Treg Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Total Bilirubin ◽  
Study Group ◽  
Related Factors ◽  
Tnf Α

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

scholarly journals PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Min Thura ◽  
Zu Ye ◽  
Abdul Qader Al-Aidaroos ◽  
Qiancheng Xiong ◽  
Jun Yi Ong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Cancer Cells ◽  
Embryonic Stem ◽  
Genotoxic Stress ◽  
Stem Cell Markers ◽  
Tumor Removal ◽  
Primary Tumors ◽  
Tumor Relapse ◽  
Dna Damage Signaling

AbstractPRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis. Herein, firstly, we show that PRL3 induces Polyploid Giant Cancer Cells (PGCCs) formation. PGCCs constitute stem cell-like pools to facilitate cell survival, chemo-resistance, and tumor relapse. The correlations between PRL3 overexpression and PGCCs attributes raised possibilities that PRL3 could be involved in PGCCs formation. Secondly, we show that PRL3+ PGCCs co-express the embryonic stem cell markers SOX2 and OCT4 and arise mainly due to incomplete cytokinesis despite extensive DNA damage. Thirdly, we reveal that PRL3+ PGCCs tolerate prolonged chemotherapy-induced genotoxic stress via suppression of the pro-apoptotic ATM DNA damage-signaling pathway. Fourthly, we demonstrated PRL3-zumab, a First-in-Class humanized antibody drug against PRL3 oncotarget, could reduce tumor relapse in ‘tumor removal’ animal model. Finally, we confirmed that PGCCs were enriched in relapse tumors versus primary tumors. PRL3-zumab has been approved for Phase 2 clinical trials in Singapore, US, and China to block all solid tumors. This study further showed PRL3-zumab could potentially serve an ‘Adjuvant Immunotherapy’ after tumor removal surgery to eliminate PRL3+ PGCC stem-like cells, preventing metastasis and relapse.

scholarly journals PCGF1 promotes epigenetic activation of stemness markers and colorectal cancer stem cell enrichment

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Guangyu Ji ◽  
Wenjuan Zhou ◽  
Jingyi Du ◽  
Juan Zhou ◽  
Dong Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tumour Progression ◽  
Stem Cell Markers ◽  
Epigenetic Regulator ◽  
Cell Enrichment ◽  
Histone Trimethylation

AbstractColorectal cancer (CRC) stem cells are resistant to cancer therapy and are therefore responsible for tumour progression after conventional therapy fails. However, the molecular mechanisms underlying the maintenance of stemness are poorly understood. In this study, we identified PCGF1 as a crucial epigenetic regulator that sustains the stem cell-like phenotype of CRC. PCGF1 expression was increased in CRC and was significantly correlated with cancer progression and poor prognosis in CRC patients. PCGF1 knockdown inhibited CRC stem cell proliferation and CRC stem cell enrichment. Importantly, PCGF1 silencing impaired tumour growth in vivo. Mechanistically, PCGF1 bound to the promoters of CRC stem cell markers and activated their transcription by increasing the H3K4 histone trimethylation (H3K4me3) marks and decreasing the H3K27 histone trimethylation (H3K27me3) marks on their promoters by increasing expression of the H3K4me3 methyltransferase KMT2A and the H3K27me3 demethylase KDM6A. Our findings suggest that PCGF1 is a potential therapeutic target for CRC treatment.

Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

2018 ◽  
Vol 44 (4) ◽  
pp. 530-538
Author(s):  
Aysun Çetin ◽  
İhsan Çetin ◽  
Semih Yılmaz ◽  
Ahmet Şen ◽  
Göktuğ Savaş ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interleukin 1 ◽  
Paraoxonase 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Phenotypic Effect ◽  
Necrosis Factor Alpha ◽  
Stress Markers ◽  
Tnf Α ◽  
Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

scholarly journals The Potential of Nano Curcumin in Preventing the Formation of Artificial Antisperm Antibody in Wistar Rats through Inflammatory Pathway Regulation

2021 ◽  
Vol 9 (A) ◽  
pp. 114-118
Author(s):  
Didit Pramudhito ◽  
Suwandi Sugandi ◽  
Ida Parwati ◽  
Muchtan Sujatno ◽  
Soetojo Soetojo
Keyword(s):  
Wistar Rats ◽  
Inflammatory Cytokine ◽  
Interleukin 10 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Research Subjects ◽  
Immunological Mechanisms ◽  
Tnf Α ◽  
Pathway Regulation ◽  
Group 2

BACKGROUND: Immunological mechanisms of infertility are still poorly understood and controversial, both the cause and treatment. Inflammation, immunology, cell proliferation, cell differentiation, and cell survival are influenced by several proteins, including nuclear factor kappa-B (NFĸB), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). AIM: This study aimed to explore the potential of nano curcumin to prevent anti-sperm antibodies (ASA) formation due to the testes’ inflammatory process in Wistar rats. METHODS: This research is an experimental study with a pre-post-test approach with control group. The research subjects were rats (Rattus norvegicus) of the Wistar strain. The induced animals were grouped into three groups: Group 1 received nano curcumin 1 × 80 mg/kg BW orally, Group 2 received dexamethasone 1 × 0.3 mg/kg BW, and Group 3 received placebo aquadest 1 × 1 mL orally. TNF-α, NF-kB, and IL10 levels in serum were examined with enzyme-linked immunosorbent assay. RESULTS: The nano curcumin treatment showed the ability to reduce the pro-inflammatory cytokine protein TNF-α expression (47.3 ± 2.32) more optimally than dexamethasone treatment (54.4 ± 3.22). Nano curcumin has also shown the ability to reduce the pro-inflammatory cytokine transcription factor, NF-kB (32.5 ± 2.76) more optimally than treatment with dexamethasone (44.6 ± 2.43). CONCLUSION: Nano curcumin can prevent the formation of ASA in testicular trauma through inhibition of the inflammatory response.

scholarly journals The expression and significance of inflammatory cytokines and MMP-9 in the tears of the infected eye and contralateral uninfected eye in patients with fungal keratitis

2021 ◽  
Author(s):  
Shuang Zhang ◽  
Hui-Min Wu ◽  
Xiang-Ni Cao ◽  
Xian-Qi Zhang ◽  
Gui-ping Gao
Keyword(s):  
Tear Film ◽  
Fungal Keratitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Controls ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Healthy Control ◽  
The Relationship ◽  
Tear Film Function

Abstract Background: We investigated bilateral tear cytokine levels including interleukin (IL)-1β, IL-10, IL-17, tumor necrosis factor (TNF)-α and Matrix metalloproteinase-9 (MMP-9) in patients with fungal keratitis(FK). Meanwhile, we evaluated the relationship between the changes of tear cytokines with corneal perception and pain in infected eyes, and the relationship between tear cytokines and tear film function in contralateral uninfected eyes .Methods : A total of 60(20 FK, 20 contralateral, 20 healthy controls) tear samples were collected prospectively and analyzed by enzyme linked immunosorbent assay(ELISA). Approximately 50 to 60 ul of tear samples in each case were collected. Meanwhile ,we analyzed the changes of visual analogue scale(VAS), tear breakup time (TBUT), Schirmer I test (SIT) and corneal perception compared with healthy controls. Results :The concentrations of IL-1β, IL-10 and IL-17 increased in bilateral eyes compared with healthy controls(P<0.05). The tear concentrations of MMP-9 , TNF-α only significantly increased in affected eyes (P <0.05). Patients with FK showed significant reduction in corneal perception of infected eyes compared with controls(P<0.05). Corneal perception of the normal eyes in FK patients was slightly lower than that of control group, but there was not statistical difference (P>0.05).TBUT and SIT of contralateral uninfected eyes were significantly lower than that of control group(P<0.05), which were significantly correlated with levels of IL-1β, IL-17(P<0.05). SIT were also negatively correlated with MMP-9(P<0.05), while the levels of IL-1β, IL-10, IL-17, TNF-α and MMP-9 in the tears of the healthy control group had no significant correlation with TBUT and SIT indicators(P>0.05).The corneal perception and VAS score of the affected FK eyes showed correlation with IL-1β, IL-17 and TNF-α(P<0.05).In addition, concentration of IL-10 inversely was correlated with VAS (P<0.05). Conclusion: Proinflammatory tear cytokines are elevated in bilateral eyes with unilateral FK as associated with tear film function ,pain and corneal sensitivity.

scholarly journals Correlation between IL-10 as Cancer Biomarker and Demographic Characteristics of Colorectal Cancer Patients

2021 ◽  
pp. 1-10
Author(s):  
Rahin Sh Hamad ◽  
Bushra H. Shnawa ◽  
Shereen J. Al-Ali
Keyword(s):  
Colorectal Cancer ◽  
Pearson Correlation ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Morbidity ◽  
Serum Samples ◽  
Cancer Pathogenesis ◽  
Colorectal Cancer Patients

Colorectal cancer (CRC) is classified as one of the most prevalent cancer types worldwide, with high morbidity and mortality rates. Patients of CRC have been shown to express a detectable cytokine in serum which contributes to cancer pathogenesis. Therefore, the serum interleukin 10 (IL-10) level in CRC patients was investigated in this study. Patients' medical records with CRC admitted to the Rizgary and Nanakali hospitals, Erbil, Iraq was analyzed as the study group compared to the healthy volunteers' control group. Seventy-one serum samples were collected, thirty-one from diagnosed CRC patients and forty from healthy controls. The concentrations of IL-10 in the sera were assessed by enzyme-linked immunosorbent assay (ELISA). The present finding showed that IL-10 Was significantly elevated in CRC patients' sera compared to the control group, suggesting confirmation of its usefulness for detecting CRC patients' prognosis. A non-significant Pearson correlation was detected between IL-10 serum levels and the CRC group's age, gender, and body mass index. Herein is the first study on the evaluation of IL-10 levels in CRC patients in Kurdistan, Iraq.

scholarly journals Cytokine status in patients with myocardial infarction as a possible predictor of coronary atherosclerosis severity

2020 ◽  
Vol 19 (3) ◽  
pp. 2316
Author(s):  
O. V. Khlynova ◽  
E. A. Shishkina ◽  
N. I. Abgaryan
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Coronary Atherosclerosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Coronary Artery Atherosclerosis ◽  
Tnf Α ◽  
Atherosclerosis Severity

Aim. To study the association of cytokine status with coronary atherosclerosis severity in patients with myocardial infarction (MI).Material and methods. Between 11.2018 and 07.2019, 92 patients hospitalized with MI in Perm Clinical Cardiology Dispensary were included in the study. The control group consisted of 23 patients with stable coronary artery disease. In addition to the standard examination, enzyme-linked immunosorbent assay was used to determine the levels of interleukins (IL)-6, -10, tumor necrosis factor alpha (TNF-α), C-reactive protein.Results. Significant increase in plasma IL-6, TNF-α and C-reactive protein levels in MI patients compared with the control group. The increase in the concentration of IL-6, TNF-α, as well as the IL-6/IL-10 ratio occurs in proportion to coronary atherosclerosis severity. A direct correlation of Gensini score with IL-6, TNF-α, and IL-6/IL-10 ratio was established.Conclusion. Further study of cytokine profile parameters in MI patients will help a clearer understanding pathogenesis of coronary artery atherosclerosis. An increase in concentrations of IL-6, TNF-α, and IL-6/IL-10 ratio is associated with an increase in coronary atherosclerosis severity and can be used in practice for its prediction.

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