scholarly journals Double Lock the COVID 19: Inhibit SARS COV 2 Replication and Suppress Inflammation Cytokine Level by the Golden Compounds

2020 ◽  
Author(s):  
Zhesheng He ◽  
Chunyu Zhang ◽  
Zhongying Du ◽  
Wencong Zhao ◽  
Wenchao Niu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cell Viability ◽  
Sulfur Atom ◽  
Gold Cluster ◽  
Cytokine Level ◽  
Pharmacokinetic Studies ◽  
Down Regulation ◽  
Toxicity Studies ◽  
Tnf Α

Our studies implied the golden compounds may be more effective against COVID 19 as they synergy inhibit SARS COV 2 replication and down regulation inflammation cytokine level. Our crystal structure studies firstly revealed Au (I) ions, derived from auranofin (AF) or gold cluster (GA), covalently bind sulfur atom of Cys145 and Cys156 of Mpro of SARS COV 2. The auranofin or gold cluster well inhibit Mpro activity in vitro. Auranofin or gold cluster could well suppress inflammation cytokine level of IL 6, IL 1β, TNF α via down regulation NF κB activation in macrophage. The cell viability and rat toxicity studies show gold cluster is more safety when compared FDA approved auranofin. The rat pharmacokinetic studies of gold cluster revealed its good bioavailability.

scholarly journals Double Lock the COVID 19: Inhibit SARS COV 2 Replication and Suppress Inflammation Cytokine Level by the Golden Compounds

2020 ◽  
Author(s):  
Zhesheng He ◽  
Chunyu Zhang ◽  
Zhongying Du ◽  
Wencong Zhao ◽  
Wenchao Niu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cell Viability ◽  
Sulfur Atom ◽  
Gold Cluster ◽  
Cytokine Level ◽  
Pharmacokinetic Studies ◽  
Down Regulation ◽  
Toxicity Studies ◽  
Tnf Α

Our studies implied the golden compounds may be more effective against COVID 19 as they synergy inhibit SARS COV 2 replication and down regulation inflammation cytokine level. Our crystal structure studies firstly revealed Au (I) ions, derived from auranofin (AF) or gold cluster (GA), covalently bind sulfur atom of Cys145 and Cys156 of Mpro of SARS COV 2. The auranofin or gold cluster well inhibit Mpro activity in vitro. Auranofin or gold cluster could well suppress inflammation cytokine level of IL 6, IL 1β, TNF α via down regulation NF κB activation in macrophage. The cell viability and rat toxicity studies show gold cluster is more safety when compared FDA approved auranofin. The rat pharmacokinetic studies of gold cluster revealed its good bioavailability.

scholarly journals Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Reza Shirazinia ◽  
Ali Akbar Golabchifar ◽  
Vafa Baradaran Rahimi ◽  
Abbas Jamshidian ◽  
Alireza Samzadeh-Kermani ◽  
...  
Keyword(s):  
Cell Viability ◽  
Lead Acetate ◽  
Male Rats ◽  
Tnf Α ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
Anti Inflammatory ◽  
Opuntia Dillenii

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.

T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro

Vascular ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 314-320
Author(s):  
Weiping Ci ◽  
Tian Wang ◽  
Taotao Li ◽  
Jin Wan
Keyword(s):  
Cell Viability ◽  
Vascular Wall ◽  
Underlying Mechanism ◽  
Interleukin 8 ◽  
Control Group ◽  
Survival Fraction ◽  
Tnf Α ◽  
Significant Difference ◽  
Factor Α

Objectives The effect and underlying mechanism of T-614 (iguratimod) on Takayasu’s arteritis (TA) are unknown. Here, we report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in human aortic adventitial fibroblasts (HAAFs) in vitro and explore its initial benefit in terms of vascular wall inflammation and remodeling for patients with TA. Methods HAAFs were cultured with 0, 5, 50, 100, or 250 μg/ml T-614 in the absence or presence of tumor necrosis factor-α (TNF-α) in vitro. Cell viability was determined by a modified MTT assay. Supernatant IL-8 levels were measured by enzyme-linked immunosorbent assays. Results In the presence of TNF-α, compared to that in the control group, cell viability of HAAFs significantly decreased in the 50, 100, and 250 μg/ml T-614 treatment groups (OD value: P <  0.01, P <  0.001, P <  0.001, respectively; survival fraction (SF): P <  0.05, P <  0.001, P <  0.001, respectively). However, there was no significant difference in cell viability between TNF-α-stimulated and unstimulated groups at the same concentration of T-614. In the absence or presence of TNF-α, T-614 suppressed HAAF cell viability dose-dependently (OD value: r = −0.915, P =  0.000; r = −0.926, P =  0.000, respectively; SF: r = −0.897, P =  0.000; r = −0.885, P =  0.000, respectively). Compared to that in the control group, in the absence of TNF-α, IL-8 levels in the 5 and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.05); in the presence of TNF-α, IL-8 levels in the 5, 50, and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.001, P <  0.001, P <  0.01, respectively). Further, there was a negative correlation between supernatant IL-8 levels and T-614 concentration in groups stimulated with TNF-α ( r = −0.670, P =  0.000), but there was no significant correlation between these parameters in groups that were not stimulated with TNF-α. Conclusions In the absence or presence of TNF-α, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA.

scholarly journals Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Eun-Mi Noh ◽  
Jeong-Mi Kim ◽  
Hak Yong Lee ◽  
Hyun-Kyung Song ◽  
Sang Ok Joung ◽  
...  
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Flowering Plant ◽  
Platycodon Grandiflorum ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats. Methods For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen. Results PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage. Conclusions Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.

scholarly journals Protective Effect of Dachengqi Decoction on Pancreatic Microcirculatory in Severe Acute Pancreatitis via Down-regulating HMGB-TLR-4-IL-23-IL-17A Mediated Neutrophil Activation Though Targeting SIRT1

2021 ◽  
Author(s):  
Jia Wang ◽  
Lei Peng ◽  
Dan Chang ◽  
Da-qing Hong ◽  
Jiong Zhang
Keyword(s):  
Acute Pancreatitis ◽  
Cell Viability ◽  
Severe Acute Pancreatitis ◽  
Weight Ratio ◽  
Related Factors ◽  
Serum Lipase ◽  
Tnf Α ◽  
Wet Weight ◽  
Microcirculatory Function

Abstract BackgroundDachengqi decoction (DCQD), one of classic prescription of Chinese herbal medicine has been widely used in clinic to treat severe acute pancreatitis (SAP). The damage of pancreatic microcirculation plays key pathogenesis of SAP. However, little is known about the molecular pharmacological activity of DCQD on pancreatic microcirculation in SAP. Therefore, the purpose of the study attempted to confirm the improvement of DCQD on pancreatic microcirculation is associated with suppressing neutrophil mediated immune-inflammatory response through promoting the inactivation of HMGB1-TLR-4-IL-23-IL-17A axis via targeting the SIRT1 signal pathway in SAP.Material and MethodsSodium taurodeoxycholate and cerulein were used to establish model of SAP in vitro and vivo, respectively. The pancreatic pathological morphology, wet weight ratio, myeloperoxidase (MPO) activity, cell viability and microcirculatory function of the pancreas, as well as serum lipase and amylase expressions were evaluated. The expression levels of SIRT1, acety-HMGB1, TLR-4, HMGB1, IL-23, IL-17A, neutrophil chemokines (KC, LIX, and MIP-2), and inflammation-related factors (IL-6, IL-1β, and TNF-α), the translocation of HMGB1 and the interaction of SIRT-HMGB1 in the pancreas and serum were determined by ELISA real-time PCR, western blotting and immunoprecipitation.ResultsIn-vivo studies showed DCQD or neutralizing antibody (anti-23p19 or anti-IL-17A) could significantly decrease the activity of lipase, amylase, down-regulate the expression of CD68, MPO, wet/weight, IL-1β, IL-6, TNF-α,neutrophil chemokines (KC, LIX, MIP-2 ), alleviate pathological injury, and improve the microcirculatory function of the pancreas in rats with SAP. Moreover, DCQD remarkably augmented SIRT1 expression, promoted SIRT1 and HMGB1 combination, reduced HMGB1 translocation from nuclear to cytoplasm, and alleviated the expression of acetyl-HMGB1, HMGB1, IL-17A, TLR-4 and IL-23 in vitro and vivo with SAP. However, the intervention with EX527 (SIRT1 inhibitor) or r-HMGB1 (recombinant HMGB1) could obliviously reverse the above-mentioned influence of DCQD in SAP. In vitro, we confirmed that DCQD could decrease the acetylation, migration and release of HMGB1, and improve the decline of cell viability, SIRT1, SIRI-HMGB1 combination induced by cerulein with promoting macrophage to release IL-23 through HMGB1/TLR-4. ConclusionDCQD treatment improves SAP-induced pancreatic microcirculatory dysfunction by inhibiting neutrophil-mediated inflammation through the inactivation of HMGB1-TLR-4-IL-23-IL-17A signaling via Targeting SIRT1.Trial registration: No. 365, 2020.

scholarly journals Effects of Ropivacaine Hydrochloride on the Expression of Type I Interferon and Its Receptor in SH-SY5Y Cells

2020 ◽  
pp. 1-10
Author(s):  
Xianjie Wen ◽  
Zhaoxia Wu ◽  
Weidong Lin ◽  
Yiqun Li ◽  
Xiaoping Wang
Keyword(s):  
Cell Viability ◽  
Local Anesthetics ◽  
Type I Interferon ◽  
Inflammatory Factors ◽  
Type I ◽  
Apoptosis Rate ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Ropivacaine Hydrochloride

Nerve injury caused by local anesthetics is a hot issue that people pay close attention to, and its mechanism has not been fully clarified. Type I interferon (I-IFN) is an important factor in regulating inflammatory response. In this study, SH-SY5Y cells were injured by ropivacaine hydrochloride in vitro. The cell viability, apoptosis rate, mRNA and protein expression of I-IFN and its receptor IFNAR, as well as the contents of inflammatory cytokines TNF-α, IL-6 and IL-10 were detected to explore the correlation between I-IFN and neurotoxicity induced by ropivacaine hydrochloride. The results showed that after treated with ropivacaine hydrochloride, the cell viability was decreased, the apoptosis rate was increased, the mRNA and protein expressions of IFN-α, IFN-β, IFNAR1 and IFNAR2 were up-regulated, and the contents of inflammatory factors TNF - α, IL-6 and IL-10 were increased. These results suggest that type I interference and its receptor are associated with neurotoxicity of local anesthetics.

scholarly journals LncRNA AC008972.1 as a Novel Therapeutic Target for Prostate Cancer

2021 ◽  
Author(s):  
Jia Liu ◽  
Qijin Wu ◽  
Ruiyu Song ◽  
Wen Miao ◽  
Yuting Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Therapeutic Target ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Mouse Xenograft Model ◽  
Novel Therapeutic

Abstract Background: Prostate cancer is the leading cause of disease and death in men. Long non-coding RNAs (lncRNAs), microRNA (miRNAs) and mRNAs networks mediate prostate cancer progression. Here, we aim to investigate functions of lncRNA AC008972.1/miR-143-3p/thousand-and-one-amino acid 2 kinase (TAOK2) in prostate cancer. Methods: The expression levels of lncRNA AC008972.1, miR-143-3p and TAOK2 are detected in prostate cancer tissues and cell lines by RT-qPCR. PC3 and LNCaP cells are used to establish lncRNA AC008972.1-knockdown, miR-143-3p-overexpressing, and TAOK2-down-regulated cells. Cell viability is examined by MTT and cell proliferation is detected by clone formation assay. Cell migration and invasion are tested by wound scratch assay and transwell chamber assay. The rate of apoptosis was analyzed by flow cytometry. The protein expression is detected by western blot assay. The target is validated by RNA binding protein immunoprecipitation (RIP) assay and dual luciferase activity assay. A mouse xenograft model was conducted to investigate the oncogenic effect of lncRNA AC008972.1 on prostate cancer. Results: High expression of lncRNA AC008972.1 was associated with low overall survival in prostate cancer. Down-regulation of lncRNA AC008972.1 delayed prostate cancer process by inhibiting cell viability, proliferation, migration and invasion, as well as altering protein expression，whereas cell apoptosis was markedly promoted. LncRNA AC008972.1 negatively regulated miR-143-3p expression and miR-143-3p overexpression promoted prostate cancer process in vitro. TAOK2 expression was decreased by miR-143-3p through the complementary targeting of TAOK2 mRNA. Down-regulation of lncRNA AC008972.1 mitigated prostate cancer process in vitro based on miR-143-3p/TAOK2 node. Furthmore, the data of xenograft model experiment showed that inhibition of lncRNA AC008972.1 suppressed tumor growth in vivo. Conclusions: Collectively, knockdown of lncRNA AC008972.1 inhibits prostate cancer cell growth based on down-regulation of TAOK2 induced by miR-143-3p. Here, we identify that lncRNA AC008972.1 exerts essential roles in the progression of prostate cancer and serves as a novel therapeutic target for prostate cancer.

scholarly journals MiR-200a-3p Accelerated Hypoxia/Reoxygenation Injury in HCM Cells by Enhancing IGF2R via Wnt/β-catenin Signalling Pathway

2021 ◽  
Vol 21 (02) ◽  
Author(s):  
Yaolei Ge
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Signalling Pathway ◽  
Dependent Manner ◽  
Tnf Α ◽  
Reoxygenation Injury ◽  
Pro Inflammatory Cytokines ◽  
Hypoxia Reoxygenation

ABSTRACT The present study examined functions of miR-200a-3p accelerated progressions of HCM cells via IGF2R and Wnt/β-catenin signalling pathway after hypoxia/reoxygenation treatment in vitro. CCK-8 showed that cell viability of HCM was inhibited while apoptosis rates detected by flow cytometry were promoted in a time dependent manner after H/R (12 hours and 24 hours). Beyond that, Bcl-2 and c-IAP1 were decreased but Bax and caspase-3 were upregulated by H/R treatment. IL-1β, IL-6, TNF-α and NLRP3 were also increased after treatment. RT-qPCR showed increased expressions of miR-200a-3p by H/R treatment while its inhibitor elevated cell viability but depressed apoptosis rate and pro-inflammatory cytokines’ expressions. IGF2R was upregulated after H/R treatment and its downregulation magnified effects of suppressed miR-200a-3p. HIF-1α/Wnt/β -catenin signalling pathway was activated by miR-200a-3p and IGF2R while IWP-2 treatment abolished the activation of Wnt3a andβ -catenin, causing decreased apoptosis and pro-inflammatory cytokines’ expressions but accelerated the cell viability.

scholarly journals KCNQ1OT1 promotes the proliferation and migration of psoriatic keratinocytes by regulating miR-183-3p/GAB1

2021 ◽  
Vol 49 (5) ◽  
pp. 125-130
Author(s):  
Ting Liu ◽  
Xi Duan ◽  
Jia He ◽  
Chuan Yang
Keyword(s):  
Cell Viability ◽  
Cell Model ◽  
Growth Factor Receptor ◽  
Keratinocyte Proliferation ◽  
Tnf Α ◽  
Keratinocyte Cell Line Hacat ◽  
Gated Channel ◽  
And Migration ◽  
Proliferation And Migration

Background: Differentially expressed lncRNAs have been reported to be involved in keratinocyte proliferation and migration, and participate in the development of psoriasis. Potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) was implicated in the pathogenesis of various diseases, including cancer, sepsis, diabetic cardiomyopathy, and atherosclerosis. The influence of KCNQ1OT1 on proliferation and migration of psoriatic keratinocytes was unfolded in this study. Methods: Human keratinocyte cell line (HaCaT) was incubated with TNF-α to establish in vitro cell model of psoriasis. Cell viability and migration were assessed by MTT and wound healing, respectively. Target miRNA of KCNQ1OT1 was identified by luciferase activity and RNA immunoprecipitation (RIP) assays. Results: KCNQ1OT1 was up-regulated in TNF-α-induced HaCaT, and knockdown of KCNQ1OT1 reduced cell viability and suppressed migration of TNF-α-induced HaCaT. KCNQ1OT1 bind to miR-183-3p and negatively regulated expression of miR-183-3p. Over-expression of GAB1 (growth factor receptor binding 2-associated binding protein 1) counteracted with the suppressive effects of KCNQ1OT1 silence on cell viability and migration of TNF-α-induced HaCaT. Conclusion: Silence of KCNQ1OT1 suppressed proliferation and migration of TNF-α-induced HaCaT through regulation of miR-183-3p/GAB1, providing potential strategy for psoriasis.

Sign in / Sign up

Export Citation Format

Share Document