lps-atp-induced-death-pma-differentiated-thp-1-macrophages-its

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Cell death is a fundamental process in all living organisms. The protocol establishes a lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced ...

Allergic rhinitis (AR) is a non-infectious chronic nasal mucosal disease mediated mainly by IgE, which affects 40% of the global population and has a recurrence rate of more than 50%. The modified Yupingfeng formula (MYPFF) is widely used in the treatment of allergic rhinitis in China. However, there is no evidence-based medical evidence for the efficacy and safety of MYPFF in the treatment of allergic rhinitis.

Efficacy and safety of modified Yupingfeng formula in treating allergic rhinitis: A protocol for systematic review and meta analysis.

Histone deacetylases (HDACs) play a key role in the homeostasis of protein acetylation in histones and have recently emerged as a therapeutic target for numerous diseases. The inhibition of HDACs may block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumour cells. Thus, HDAC inhibitors (HDACi) have received increasing attention and many of which are developed from natural sources. In the past few decades, naturally occurring HDACi have been identified to have potent anticancer activities, some of which have demonstrated promising therapeutic effects on haematological malignancies. In this review, we summarized the discovery and modification of HDAC inhibitors from natural sources, novel drug design that uses natural products as parent nuclei, and dual target design strategies that combine HDAC with non-HDAC targets.

From natural products to HDAC inhibitors: An overview of drug discovery and design strategy.

The objective of this study was to clarify the species differences of metabolic stability of E28 in liver microsomes, and to study metabolic phenotypes of E28 in human liver microsomes by chemical inhibition method.The metabolites in plasma, urine, and faeces samples from mice received caudal vein intravenous were detected and identified by UHPLC-HRMS, and the tissue distribution was studied after oral administration.E28 was metabolised rapidly in liver microsomes of each species with a short half-live T and a moderate clearance, except for rats. The metabolic properties of E28 were similar in human and mouse liver microsomes. Data from metabolic phenotype studies indicated that CYP2D6, CYP3A4 and CYP2C9 were the main metabolic enzymes participating in the metabolism of E28.The main metabolic pathways implicated include oxidation, methylation, amide hydrolysis, acetylation, glucuronide conjugation.Tissue distribution studies showed that E28 could be detected in all organs and tissues after oral administration, with the highest level in the stomach and the lowest in the brain. In bone marrow cells, the concentration of E28 in all sample points were consistently higher than its half inhibitory concentration against MV4-11 tumour cells.

Metabolic profiling in liver microsomes and mice of E28, a potent FLT3 inhibitor.

FMS-like tyrosine kinase-3 (FLT3) and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been proven to play a significant role in tumor therapy. Herein, based on the previously reported JAK2/FLT3 inhibitor 18e, we described the synthesis, structure-activity relationship and biological evaluation of a series of unique 6-(pyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridine derivatives that inhibited FLT3 and CDK4 kinases. The optimized compound 23k exhibited low nanomolar range activities with IC values of 11 and 7 nM for FLT3 and CDK4, respectively. In the MV4-11 xenograft tumor model, the tumor growth inhibition rate of 23k dosed at 200 mg/kg was 67%, suggesting that 23k possessed an antitumor therapeutic effect.

Synthesis and biological evaluation of 6-(pyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridine derivatives as novel dual FLT3/CDK4 inhibitors.

The objective of this study was to identify metabolites of PD110 by UHPLC-Q-Exactive Plus MS and determine its metabolic pathways .Mouse urine, faeces, and plasma samples were collected after an intraperitoneal administration of PD110 at a single dose of 30 mg·kg.The metabolites were detected and identified by UHPLC-Q-Exactive Plus MS and Compound Discoverer 2.0 software.In total, 44 metabolites (including 31 phase-I and 13 phase-II metabolites) were preliminarily identified according to the mass accuracy (<5 ppm) and comparison of their mass spectrometry profiles. Oxidation, glucuronide conjugation, and glucoside conjugation were the main metabolic pathways of PD110 in mice.This research first focussed on the biotransformation of PD110 in mice, and its metabolites may provide pivotal information for further pharmacological and clinical studies.

Identification of in vivo metabolites of a potential anti-rheumatoid arthritis compound, the quinazolinone derivative PD110, using ultra-high performance liquid chromatography coupled with Q-Exactive plus mass spectrometrys.

Vascular function is associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Whether exercise improves vascular function in such patients remains controversial. This study aimed to conduct a meta-analysis on the effect of exercise training on the vascular function of patients with CKD.

Association of Exercise With Vascular Function in Patients With CKD: A Meta-Analysis of Randomized Controlled Trials.

The assembly of inflammasomes drives caspase-1 activation, which further promotes proinflammatory cytokine secretion and downstream pyroptosis. The discovery of novel caspase-1 inhibitors is pivotal to developing new therapeutic means for inflammasome-involved diseases. In our present study, sennoside A (Sen A), a popular ingredient in multiple weight-loss medicines and dietary supplements, is found to potently inhibit the enzymatic activity of caspase-1 . Sen A considerably decreased IL-1β production in macrophages stimulated by LPS plus ATP, nigericin or MSU as well as poly(dA:dT) transfection, and remedied ROS-involved pyroptosis  caspase-1 inhibition. Mechanistically, Sen A not only suppressed the assembly of both NLRP3 and AIM2 inflammasome but also affected the priming process of NLRP3 inflammasome by blocking NF-κB signaling. Sen A significantly ameliorated the pathophysiological effect in LPS-, MSU- and carrageenan-challenged rodent models by suppressing inflammasome activation. Furthermore, P2X7 was indispensable for Sen A inhibiting NLRP3 inflammasome since it failed to further decrease IL-1β and IL-18 production in LPS plus ATP-stimulated BMDMs that were transfected with P2X7 siRNA. Sen A also restrained the large pore-forming functionalities of the P2X7R as verified by the YO-PRO-1 uptake assay. Taken together, Sen A inactivates caspase-1 to inhibit NLRP3 and AIM2 inflammasome-involved inflammation in a P2X7-dependent manner, making it an attractive candidate as a caspase-1 small-molecular inhibitor.

Sennoside A is a novel inhibitor targeting caspase-1.

Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, and IL-17, with characteristics of the cytokine storm (CS). Although recently studied cytokine inhibitors are considered as potent and targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough. Interestingly, certain isoquinoline alkaloids in  Franch. (CCFIAs) exerted a multitude of biological activities such as anti-inflammatory, antioxidant, antibacterial, and immunomodulatory etc, revealing a great potential for calming CS. Therefore, in this timeline review, we report and compare the effects of CCFIAs to attenuate the exacerbation of inflammatory responses by modulating signaling pathways like NF-ĸB, mitogen-activated protein kinase, JAK/STAT, and NLRP3. In addition, we also discuss the role of berberine (BBR) in two different triggers of CS, namely sepsis and viral infections, as well as its clinical applications. These evidence provide a rationale for considering CCFIAs as therapeutic agents against inflammatory CS and this suggestion requires further validation with clinical studies.

Cytokine storm-calming property of the isoquinoline alkaloids in  Franch.

Persistent inflammation has been recognized as an important comorbid condition in patients with chronic kidney disease (CKD) and is associated with many complications, mortality, and progression of CKD. Previous studies have not drawn a clear conclusion about the anti-inflammatory effects of statins in CKD. This meta-analysis is aimed at assessing the anti-inflammatory effects of statins therapy in patients with CKD.

Statins Have an Anti-Inflammation in CKD Patients: A Meta-Analysis of Randomized Trials.

Progressive cerebral venous sinus thrombosis (CVST)-induced visual loss remains problematic, despite decreasing overall mortality owing to early diagnosis and aggressive treatment. Optic nerve sheath fenestration (ONSF) improves or stabilizes visual function in patients with idiopathic intracranial hypertension; however, its role in CVST awaits elucidation. We evaluated the efficacy and safety of ONSF in resolving CVST-induced visual impairment based on long-term observation.

Optic Nerve Sheath Fenestration for Progressive Visual Loss in Cerebral Venous Sinus Thrombosis: A Long-Term Retrospective Observational Study.

In recent years, an increasing number of scientists have focused on conducting experiments on laser ablation of bone tissue. The purpose of this study was to summarize the prognosis of tissue and the extent of thermal damage in past hard tissue ablation experiments, and review the evidence for the feasibility of laser osteotomy in surgery. An electronic search of PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science (WOS) for relevant English-language articles published through June 2023 was conducted. This review includes 48 literature reports on laser ablation of hard tissues from medical and biological perspectives. It summarizes previous studies in which the ideal ablation rate, depth of ablation, and minimal damage to bone tissue and surrounding soft tissues were achieved by changing the laser type, optimizing the laser parameter settings, or adding adjuvant devices. By observing their post-operative healing and inflammatory response, this review aims to provide a better understanding of pulsed laser ablation of hard tissues. Previous studies suggest that laser osteotomy has yielded encouraging results in bone resection procedures. We believe that low or even no thermal damage can be achieved by experimentally selecting a suitable laser type, optimizing laser parameters such as pulse duration and frequency, or adding additional auxiliary cooling devices. However, the lack of clinical studies makes it difficult to conclusively determine whether laser osteotomy is superior in clinical applications.

Thermal damage and the prognostic evaluation of laser ablation of bone tissue-a review.

 Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine combined with montelukast in the treatment of AR. This study aimed to evaluate the efficacy and safety of the loratadine-montelukast combination on AR.  In this meta-analysis, searches were conducted on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure (CNKI). The search terms included loratadine, montelukast, allergic rhinitis, and clinical trials. Meta-analyses were conducted using Rev Man 5.3 and Stata 15 statistical software.  A total of 23 studies with 4,902 participants were enrolled. For the primary outcome, pooled results showed that loratadine-montelukast can significantly reduce total nasal symptom scores (TNSS), when compared with loratadine (SMD, -1.00; 95% CI, -1.35 to -0.65,  < 0.00001), montelukast (SMD, -0.46; 95% CI, -0.68 to -0.25,  < 0.0001), or placebo (SMD, -0.93; 95% CI, -1.37 to -0.49,  < 0.00001). For secondary outcomes, pooled results showed that compared with loratadine, loratadine-montelukast can significantly improve nasal congestion, nasal itching, nasal sneezing, nasal rhinorrhea, and rhinoconjunctivitis quality of life questionnaires (RQLQ). Compared with montelukast, loratadine-montelukast can significantly improve nasal itching, and nasal sneezing. Compared with placebo, loratadine-montelukast can significantly improve nasal congestion, and RQLQ.  Loratadine-montelukast combination is superior to loratadine monotherapy, montelukast monotherapy, or placebo in improving AR symptoms. Therefore, loratadine-montelukast combination can be an option for patients with moderate-severe AR or poorly response to monotherapy. Systematic review registration number: clinicaltrials.gov, identifier CRD42023397519.

A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis.

 Hyaluronic acid (HA), the main component of the extracellular matrix, has the ability to promote tissue repair and regulate inflammation. It is used in otolaryngology as an adjuvant treatment to alleviate postoperative nasal symptoms. However, there is currently insufficient evidence demonstrating the therapeutic efficacy of HA for patients with nasal inflammatory diseases (NIDs). Therefore, this study aimed to evaluate the efficacy and safety of topical HA in the treatment of NID patients without receiving surgery.  In this meta-analysis, comprehensive searches were conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science. Keywords searched included "hyaluronic acid," "sinusitis," "allergic rhinitis," "rhinitis," and "randomized controlled trials (RCTs)." The Cochrane Collaboration's "Risk of Bias Assessment" tool was used to assess the quality of the included trials, and the meta-analysis was performed using the RevMan 5.3 and STATA 15 statistical software.  A total of 11 articles and 825 participants were enrolled. For the primary outcomes, the pooled results revealed that HA significantly improves nasal obstruction (SMD, -0.53; 95% CI, -0.92 to -0.14;  = 0.008; and I = 79%) and rhinorrhea (SMD, -0.71; 95% CI, -1.27 to -0.15;  = 0.01; and I = 90%) in patients with NIDs. As for the secondary outcomes, the pooled results demonstrated that when compared with the control group, HA could significantly improve nasal endoscopic scores ( < 0.05), rhinitis scores ( < 0.05), rhinomanometry ( < 0.05), nasal neutrophils ( < 0.05), and mucociliary clearance ( < 0.05). However, no significant differences were observed between the two groups regarding nasal itching, sneezing, hyposmia, quality-of-life scores, and nasal eosinophils. For the risk of bias, 54.5% and 45.5% of trials had a low risk of bias in the randomization process and deviation of the intended intervention, respectively.  In the present study, the results reveal that HA might ameliorate symptoms of patients with NIDs. However, more clinical trials with larger participant cohorts are required to confirm this result.  clinicaltrials.gov, identifier CRD42023414539.

Efficacy of hyaluronic acid in the treatment of nasal inflammatory diseases: a systematic review and meta-analysis.

A drug pair is a fundamental aspect of traditional Chinese medicine prescriptions. Scutellaria baicalensis Georgi and Coptis chinensis Franch, commonly used as an herb couple (SBCC), are representative heat-clearing and dampness-drying drugs. They possess functions such as clearing heat, drying dampness, purging fire, and detoxifying. These herbs are used in both traditional and modern medicine for treating inflammation.

The Scutellaria-Coptis herb couple and its active small-molecule ingredient wogonoside alleviate cytokine storm by regulating the CD39/NLRP3/GSDMD signaling pathway.

Article	Year
Efficacy and safety of modified Yupingfeng formula in treating allergic rhinitis: A protocol for systematic review and meta analysis. Medicine\| PubMed ID: 33371114	2020
From natural products to HDAC inhibitors: An overview of drug discovery and design strategy. Bioorganic & medicinal chemistry\| PubMed ID: 34826681	2021
Metabolic profiling in liver microsomes and mice of E28, a potent FLT3 inhibitor. Xenobiotica; the fate of foreign compounds in biological systems\| PubMed ID: 35078381	2022
Synthesis and biological evaluation of 6-(pyrimidin-4-yl)-1H-pyrazolo[4,3-b]pyridine derivatives as novel dual FLT3/CDK4 inhibitors. Bioorganic chemistry\| PubMed ID: 35180490	2022
Identification of in vivo metabolites of a potential anti-rheumatoid arthritis compound, the quinazolinone derivative PD110, using ultra-high performance liquid chromatography coupled with Q... Xenobiotica; the fate of foreign compounds in biological systems\| PubMed ID: 35377274	2022
Association of Exercise With Vascular Function in Patients With CKD: A Meta-Analysis of Randomized Controlled Trials. Frontiers in medicine\| PubMed ID: 35872793	2022
Sennoside A is a novel inhibitor targeting caspase-1. Food & function\| PubMed ID: 36097956	2022
Cytokine storm-calming property of the isoquinoline alkaloids in Franch. Frontiers in pharmacology\| PubMed ID: 36147356	2022
Statins Have an Anti-Inflammation in CKD Patients: A Meta-Analysis of Randomized Trials. BioMed research international\| PubMed ID: 36317110	2022
Optic Nerve Sheath Fenestration for Progressive Visual Loss in Cerebral Venous Sinus Thrombosis: A Long-Term Retrospective Observational Study. Neurology and therapy\| PubMed ID: 36609961	2023
Thermal damage and the prognostic evaluation of laser ablation of bone tissue-a review. Lasers in medical science\| PubMed ID: 37676517	2023
A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis. Frontiers in pharmacology\| PubMed ID: 37915414	2023
Efficacy of hyaluronic acid in the treatment of nasal inflammatory diseases: a systematic review and meta-analysis. Frontiers in pharmacology\| PubMed ID: 38384292	2024
The Scutellaria-Coptis herb couple and its active small-molecule ingredient wogonoside alleviate cytokine storm by regulating the CD39/NLRP3/GSDMD signaling pathway. Journal of ethnopharmacology\| PubMed ID: 38593962	2024

Huan Wang

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