The Role of Macrophages in the Development of Acute and Chronic Inflammatory Lung Diseases

Cells, Год журнала: 2021, Номер 10(4), С. 897 - 897

Опубликована: Апрель 14, 2021

Macrophages play an important role in the innate and adaptive immune responses of organ systems, including lungs, to particles pathogens. Cumulative results show that macrophages contribute development progression acute or chronic inflammatory through secretion cytokines/chemokines activation transcription factors pathogenesis lung diseases, such as injury (ALI), respiratory distress syndrome (ARDS), ARDS related COVID-19 (coronavirus disease 2019, caused by severe coronavirus 2 (SARS-CoV-2)), allergic asthma, obstructive pulmonary (COPD), idiopathic fibrosis (IPF). This review summarizes functions their associated underlying mechanisms ALI, ARDS, COVID-19-related COPD, IPF briefly introduces experimental animal models. Thus, this suggests effective therapeutic approach focuses on regulation macrophage function context diseases.

Язык: Английский

---

PM2.5 Exposure and Asthma Development: The Key Role of Oxidative Stress

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 12

Опубликована: Апрель 4, 2022

Oxidative stress is defined as the imbalance between reactive oxygen species (ROS) production and endogenous antioxidant defense system, leading to cellular damage. Asthma a common chronic inflammatory airway disease. The presence of asthma tends increase (ROS), system in lungs insufficient mitigate it. Therefore, can lead an exacerbation hyperresponsiveness inflammation. PM2.5 exposure increases ROS levels. Meanwhile, accumulation will further enhance oxidative response, resulting DNA, protein, lipid, other molecular damage, respiratory diseases. An in-depth study on relationship PM2.5-related helpful understand pathogenesis progression disease provides new direction for treatment This paper reviews research progress PM2.5-induced well highlights therapeutic potentials approaches asthma.

Язык: Английский

---

Structure-Based Virtual Screening for Ligands of G Protein–Coupled Receptors: What Can Molecular Docking Do for You?

Pharmacological Reviews, Год журнала: 2021, Номер 73(4), С. 1698 - 1736

Опубликована: Окт. 1, 2021

G protein–coupled receptors (GPCRs) constitute the largest family of membrane proteins in human genome and are important therapeutic targets. During last decade, number atomic-resolution structures GPCRs has increased rapidly, providing insights into drug binding at molecular level. These breakthroughs have created excitement regarding potential using structural information ligand design initiated a new era rational discovery for GPCRs. The docking method is now widely applied to model three-dimensional GPCR-ligand complexes screen chemical probes large compound libraries. In this review article, we first summarize current coverage GPCR superfamily understanding receptor-ligand interactions atomic resolution. We then present general workflow structure-based virtual screening strategies discover ligands assess state art research field by summarizing prospective applications based on experimental structures. Strategies identify compounds with specific efficacy selectivity profiles discussed, illustrating opportunities limitations method. Our overview shows that can novel leads will be essential pursuing next generation drugs.

Significance Statement

Extraordinary advances biology revealed details recognition targets, avenues design. Structure-based an efficient computational approach from libraries, which accelerate development candidates.

Язык: Английский

---

Study effect of probiotics and prebiotics on treatment of OVA-LPS-induced of allergic asthma inflammation and pneumonia by regulating the TLR4/NF-kB signaling pathway

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Март 16, 2022

Abstract Asthma is a common respiratory disease, and immune system dysregulation has direct relevance to asthma pathogenesis. Probiotics prebiotics have immunomodulatory effects can regulate responses may attenuate allergic reactions. Therefore, in this study, we explored the role of probiotics regulating acute airway inflammation TLR4/NF-kB pathway. Allergic model BALB/c mice was produced treated with (LA-5, GG, BB-12) (FOS GOS). Then AHR, BALF cells count, EPO activity, IL-4, 5, 13, 17, 25, 33, as well IFN-γ, total OVA-specific IgE, IgG1, Cys-LT, LTB4, LTC4, TSLP levels were measured. Also, GTP/GOT assay performed gene expression Akt, NLR3, NF-kB, PI3K, MyD88, TLR4, CCL11, CCL24, MUC5a, Eotaxin, IL-38, IL-8 determined. Finally, lung histopathological features evaluated. Treatment could control eosinophil infiltration reduce immunoglobulins, IL-17, GTP also decrease mucus secretion, goblet cell hyperplasia, peribronchial perivascular also, activity. It TLR4 CCL11. On other hand, IL-38 increased by both probiotic prebiotic treatment. leukotrienes, AKT, NF-κB, MUC5a. The treatment PI3K expression. Both treatments had no significant effect on GOT, IL-8, eotaxin CCL24 induce tolerance allegro-inflammatory reactions alter conditions. modulate cellular humoral prevent disorders.

Язык: Английский

---

Airway hyperresponsiveness in asthma: The role of the epithelium

Journal of Allergy and Clinical Immunology, Год журнала: 2024, Номер 153(5), С. 1181 - 1193

Опубликована: Фев. 21, 2024

Airway hyperresponsiveness (AHR) is a key clinical feature of asthma. The presence AHR in people with asthma provides the substrate for bronchoconstriction response to numerous diverse stimuli, contributing airflow limitation and symptoms including breathlessness, wheeze, chest tightness. Dysfunctional airway smooth muscle significantly contributes displayed as increased sensitivity direct pharmacologic bronchoconstrictor such inhaled histamine methacholine (direct AHR), or endogenous mediators released by activated cells mast (indirect AHR). Research vivo human models has shown that disrupted epithelium plays an important role driving inflammation mediates indirect through release cytokines thymic stromal lymphopoietin IL-33. These upregulate type 2 promoting eosinophilia induce from histamine, prostaglandin D

Язык: Английский

---

Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes

European Journal of Medicinal Chemistry, Год журнала: 2020, Номер 193, С. 112238 - 112238

Опубликована: Март 17, 2020

Язык: Английский

---

PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma

Inflammation, Год журнала: 2021, Номер 44(5), С. 1895 - 1907

Опубликована: Апрель 16, 2021

Язык: Английский

---

Anti-Viral and Immunomodulatory Properties of Propolis: Chemical Diversity, Pharmacological Properties, Preclinical and Clinical Applications, and In Silico Potential against SARS-CoV-2

Foods, Год журнала: 2021, Номер 10(8), С. 1776 - 1776

Опубликована: Июль 31, 2021

Propolis, a resin produced by honeybees, has long been used as dietary supplement and folk remedy, more recent preclinical investigations have demonstrated large spectrum of potential therapeutic bioactivities, including antioxidant, antibacterial, anti-inflammatory, neuroprotective, immunomodulatory, anticancer, antiviral properties. As an agent, propolis various constituents shown promising efficacy against adenoviruses, influenza viruses, respiratory tract herpes simplex virus type 1 (HSV-1) 2 (HSV-2), human immunodeficiency (HIV), severe acute syndrome coronavirus (SARS-CoV-2). Over 300 chemical components identified in propolis, terpenes, flavonoids, phenolic acids, with the specific constituent profile varying widely according to geographic origin regional flora. Propolis its SARS-CoV-2 modulating multiple pathogenic pathways. Molecular docking studies high binding affinities derivatives proteins, 3C-like protease (3CLpro), papain-like (PLpro), RNA-dependent RNA polymerase (RdRp), receptor-binding domain (RBD) spike protein (S-protein), helicase (NSP13), well viral target angiotensin-converting enzyme (ACE2). Among these compounds, retusapurpurin A affinity 3CLpro (ΔG = −9.4 kcal/mol), RdRp (−7.5), RBD (−7.2), NSP13 (−9.4), ACE2 (−10.4) potent inhibition entry forming hydrogen bonds amino acid residues within proteins. In addition, propolis-derived baccharin even higher towards PLpro (−8.2 kcal/mol). Measures drug-likeness parameters, metabolism, distribution, absorption, excretion, toxicity (ADMET) characteristics, also support effective agent combat COVID-19.

Язык: Английский

---

MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease

Frontiers in Immunology, Год журнала: 2021, Номер 11

Опубликована: Янв. 8, 2021

Chronic respiratory diseases (CRDs) are an important factor of morbidity and mortality, accounting for approximately 6% total deaths worldwide. The main CRDs asthma chronic obstructive pulmonary disease (COPD). These complex have different triggers including allergens, pollutants, tobacco smoke, other risk factors. It is to highlight that although incurable, various forms treatment improve shortness breath quality life. search tools can ensure accurate diagnosis crucial. MicroRNAs (miRNAs) small non-coding RNAs been described as promising diagnostic therapeutic biomarkers CRDs. They implicated in multiple processes COPD, regulating pathways associated with inflammation, thereby showing miRNAs critical regulators the immune response. Indeed, found be deregulated several biofluids (sputum, bronchoalveolar lavage, serum) both structural lung cells patients comparison healthy subjects, their potential role biomarkers. Also, play a part development or termination histopathological changes comorbidities, revealing complexity miRNA regulation opening up new possibilities. Finally, proposed prognostic response conventional biologic treatments miRNA-based has emerged approach clinical intervention these diseases; however, this field still development. present review applies systems biology understanding regulatory networks summarizing roles pathophysiology, diagnosis, treatment.

Язык: Английский

---

Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases

Pharmacological Research, Год журнала: 2022, Номер 187, С. 106566 - 106566

Опубликована: Ноя. 21, 2022

Colony-stimulating factor-1 receptor (CSF-1R), also known as FMS kinase, is a type I single transmembrane protein mainly expressed in myeloid cells, such monocytes, macrophages, glial and osteoclasts. The endogenous ligands, colony-stimulating (CSF-1) Interleukin-34 (IL-34), activate CSF-1R downstream signaling pathways including PI3K-AKT, JAK-STATs, MAPKs, modulate the proliferation, differentiation, migration, activation of target immune cells. Over past decades, promising therapeutic potential inhibition has been widely studied for decreasing suppression escape tumors, owing to depletion reprogramming tumor-associated macrophages. In addition, excessive inflammatory diseases consecutively uncovered recent years, which may result inflammation bone, kidney, lung, liver central nervous system. Agents against have increasingly investigated preclinical or clinical studies treatment. However, pathological mechanism indistinct whether can be identified biomarkers remains controversial. With background information aforementioned, this review focus on dialectical roles its ligands regulating innate cells highlights various implications blocking diseases.

Язык: Английский

---