In vitro and in vivo relaxation and anti-inflammation of natural flavonoids from Elaeagnus pungens leaf via L-type calcium channel and targeting MAPK signal pathway

Remimazolam is a new benzodiazepine of sedative drugs with an ultra-short-acting anesthetic effect, commonly used for critically ill patients (especially septic patients) in intensive care units (ICUs). Although some anesthetics have been reported to show certain anti-inflammatory effects, the role of remimazolam in inflammation is still remained unknown. Here, we studied the effects of remimazolam on macrophage in response to LPS both in vivo and in vitro. Interestingly, compared with LPS treatment group, remimazolam remarkably improved survival rate of endotoxemia mice and decreased the release of LPS-induced inflammatory mediators (such as TNF-α, IL-6, and IL-1β). We further found that remimazolam not only inhibited the activation of MAPK signal pathway at 15 min after LPS treatment but also disturbed Rab5a related TLR4 expression at cell surface in response to LPS at a later time. Such evidence suggests that remimazolam might be beneficial to septic patients who are suffering from uncontrolled inflammatory responses.

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Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

Reviews on Environmental Health ◽

10.1515/reveh-2020-0026 ◽

2020 ◽

Vol 35 (3) ◽

pp. 233-238

Author(s):

Muflihatul Muniroh

Keyword(s):

Inflammatory Cytokines ◽

Health Concern ◽

Brain Cells ◽

Preventive Strategy ◽

Hearing Impairments ◽

Sensory Disturbances ◽

Anti Inflammation ◽

Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

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Ginkgolic acid induces apoptosis and autophagy of endometrial carcinoma cells via inhibiting PI3K/Akt/mTOR pathway in vivo and in vitro

Human & Experimental Toxicology ◽

10.1177/09603271211023789 ◽

2021 ◽

pp. 096032712110237

Author(s):

L Zhou ◽

S Li ◽

J Sun

Keyword(s):

Endometrial Cancer ◽

B Cells ◽

Western Blot ◽

Signal Pathway ◽

Mtor Pathway ◽

Related Protein ◽

Western Blot Assay ◽

Ginkgolic Acid

Endometrial cancer (EC) is the fourth most common malignancy in women in developed countries. The prognosis of EC is extremely poor, and it is an important factor that contributes to the death of patients. Therefore, studying EC pathogenesis and therapeutic targets, and exploring effective drugs are the primary tasks to improve the prognosis of EC. In the present study, we aimed to explore the function of ginkgolic acid (GA) in EC cell apoptosis and autophagy through PI3K/Akt/mTOR signal pathway in vitro and in vivo. Firstly, MTT assay and clone formation assay were employed to analyze the Ishikawa and HEC-1-B cell viabilities and proliferation after treatment with GA. The results showed that GA inhibited endometrial cancer cell survival. Flow cytometry assay and western blot assay were applied to examine the apoptosis and apoptosis related protein Bcl-2, Bax, Cleaved caspase-3 expression levels of Ishikawa and HEC-1-B cells after treatment with GA. Next, we applied western blot assay to analyze the autophagy associated proteins LC3I, LC3II, p62 and Beclin-1 in GA treated Ishikawa and HEC-1-B cells. We found that GA promoted apoptosis and induced autophagy of endometrial cancer cells. Meanwhile, western blot assay was also used to determine the expression levels of the PI3K/Akt/mTOR signal pathway related protein and the results revealed that GA inhibited the activity of PI3K/Akt/mTOR pathway. Finally, we found that GA inhibited tumor growth in vivo through immunohistochemistry assay. In conclusion, GA induces apoptosis and autophagy of EC cells via inhibiting PI3K/Akt/mTOR pathway in vivo and vitro.

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Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo

Food & Function ◽

10.1039/d0fo02325f ◽

2021 ◽

Author(s):

Ding-Chao Zhu ◽

Yi-Han Wang ◽

Jia-Hao Lin ◽

Zhi-Min Miao ◽

Jia-Jing Xu ◽

...

Keyword(s):

Cartilage Degeneration ◽

Degenerative Joint Disease ◽

Signal Pathway ◽

Joint Disease ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Articular Cartilage Degeneration

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and...

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Formulation and In vitro/In vivo Evaluation of Buccoadhesive Discs for Controlled Release of Calcium Channel Antagonist

American Journal of Drug Discovery and Development ◽

10.3923/ajdd.2014.210.231 ◽

2014 ◽

Vol 4 (4) ◽

pp. 210-231 ◽

Cited By ~ 2

Author(s):

Mohamed Haider ◽

Magdy Mohamed ◽

Muaadh Ali

Keyword(s):

Controlled Release ◽

Calcium Channel ◽

Calcium Channel Antagonist ◽

In Vivo Evaluation

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Identification and characterization of a novel adiponectin receptor agonist adipo anti‐inflammation agonist and its anti‐inflammatory effects in vitro and in vivo

British Journal of Pharmacology ◽

10.1111/bph.15277 ◽

2020 ◽

Vol 178 (2) ◽

pp. 280-297

Author(s):

Wei Qiu ◽

Hongle Wu ◽

Zhekai Hu ◽

Xingwen Wu ◽

Maxwell Tu ◽

...

Keyword(s):

Receptor Agonist ◽

Adiponectin Receptor ◽

Anti Inflammatory ◽

Identification And Characterization ◽

Anti Inflammation

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Anti-inflammatory effects of Hederacoside-C on Staphylococcus aureus induced inflammation via TLRs and their downstream signal pathway in vivo and in vitro

Microbial Pathogenesis ◽

10.1016/j.micpath.2019.103767 ◽

2019 ◽

Vol 137 ◽

pp. 103767 ◽

Cited By ~ 4

Author(s):

Muhammad Akhtar ◽

Aftab Shaukat ◽

Arshad Zahoor ◽

Yu Chen ◽

Ying Wang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Signal Pathway ◽

Anti Inflammatory

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Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01742-4 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Mu-Su Pan ◽

Hui Wang ◽

Kamar Hasan Ansari ◽

Xin-Ping Li ◽

Wei Sun ◽

...

Keyword(s):

Tumor Growth ◽

Gallbladder Cancer ◽

Molecular Mechanism ◽

Poor Prognosis ◽

Vasculogenic Mimicry ◽

Tube Formation ◽

Signal Pathway ◽

Cancer Associated Fibroblasts

Abstract Background Cancer-associated fibroblasts (CAFs) and vasculogenic mimicry (VM) play important roles in the occurrence and development of tumors. However, the relationship between CAFs and VM formation, especially in gallbladder cancer (GBC) has not been clarified. In this study, we investigated whether gallbladder CAFs (GCAFs) can promote VM formation and tumor growth and explored the underlying molecular mechanism. Methods A co-culture system of human GBC cells and fibroblasts or HUVECs was established. VM formation, proliferation, invasion, migration, tube formation assays, CD31-PAS double staining, optic/electron microscopy and tumor xenograft assay were used to detect VM formation and malignant phenotypes of 3-D co-culture matrices in vitro, as well as the VM formation and tumor growth of xenografts in vivo, respectively. Microarray analysis was used to analyze gene expression profile in GCAFs/NFs and VM (+)/VM (−) in vitro. QRT-PCR, western blotting, IHC and CIF were used to detected NOX4 expression in GCAFs/NFs, 3-D culture/co-culture matrices in vitro, the xenografts in vivo and human gallbladder tissue/stroma samples. The correlation between NOX4 expression and clinicopathological and prognostic factors of GBC patients was analyzed. And, the underlying molecular mechanism of GCAFs promoting VM formation and tumor growth in GBC was explored. Results GCAFs promote VM formation and tumor growth in GBC; and the finding was confirmed by facts that GCAFs induced proliferation, invasion, migration and tube formation of GBC cells in vitro, and promoted VM formation and tumor growth of xenografts in vivo. NOX4 is highly expressed in GBC and its stroma, which is the key gene for VM formation, and is correlated with tumor aggression and survival of GBC patients. The GBC patients with high NOX4 expression in tumor cells and stroma have a poor prognosis. The underlying molecular mechanism may be related to the upregulation of NOX4 expression through paracrine IL-6 mediated IL-6/JAK/STAT3 signaling pathway. Conclusions GCAFs promote VM formation and tumor growth in GBC via upregulating NOX4 expression through the activation of IL-6-JAK-STAT3 signal pathway. NOX4, as a VM-related gene in GBC, is overexpressed in GBC cells and GCAFs, which is related to aggression and unfavorable prognosis of GBC patients.

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