Inflammation In Pulmonary Disease Research Articles

Evaluation of vitamin D deficiency and low bone mass in children with asthma in fars province: A case-control study.

Asthma is a chronic inflammatory pulmonary disease which affects 10%-20% of children and adolescents. Inhaled corticosteroids (ICS) is one of its most effective therapies. The effect of systemic corticosteroids on decreasing bone mineral density (BMD) was investigated and proved in children; however, the influence of ICSs on bone density has still remained unclear. This study evaluates the bone mineral density of children and adolescents with asthma in southern Iran and the associated factors, for example, amount of used inhaled steroid. This case-control study enrolled 41 children and adolescents (aged 8-18 years) with asthma and their age and gender-matched controls in 2019-2020. Serum Calcium, phosphate, vitamin D, and bone mineral density were measured. Their physical activity, sun exposure, and fracture history were evaluated subjectively. Lumbar BMD and BMD Z-score in patients showed no significant difference with controls (p = 0.23, p = 0.73). Also, it showed that there was no significant difference in biochemical studies, growth, and bone densitometry parameters between patients who used ICSs for less than 3 months/year corticosteroid therapy compared to those with equal or more than 3 months/year usage. Prevalence of vitamin D deficiency was 28% and 8% in the controls and patients, respectively (p = 0.005). The present study showed that 9.46% of children and adolescents with asthma had low bone mass for chronological age, and it is not significantly higher than normal population. Dosage of inhaled steroid did not associate with osteoporosis in these patients. Prevalence of vitamin D deficiency in patients was lower than normal population, probably due to receiving vitamin D in their routine follow-ups.

Fatty acids metabolism in ozone-induced pulmonary inflammatory injury: Evidence, mechanism and prevention

Ozone (O3) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O3-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O3 (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3−/−) mice to explore the mechanism of O3-induced lung fatty acid metabolism disorder. Results demonstrated that O3 exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O3 exposure. Additionally, LKB1 overexpression alleviated O3-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 −/− mice compared with those in wide type mice after O3 exposure. Furthermore, administrating DGLA intratracheally prior to O3 exposure significantly attenuated O3-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O3-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.

Association between systemic inflammatory markers and chronic obstructive pulmonary disease: A population-based study

ObjectiveTo investigate whether inflammatory indices, including the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), product of platelet and neutrophil count (PPN), and lymphocyte-to-monocyte ratio (LMR), correlate with chronic obstructive pulmonary disease (COPD). MethodsThis was a cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) database 2007–2018. The SII, NLR, PLR, PPN and LMR were calculated based on blood cell counts and were log2-transformed. COPD was diagnosed via a questionnaire or spirometry examination. Multivariate logistic regression, sensitivity analysis, subgroup analyses, and interaction tests were performed to evaluate the relationships. Results23,875 participants, including 1000 COPD patients (453 diagnosed via spirometry examination, 547 diagnosed via a questionnaire), were enrolled in this study. Positive associations were observed between SII (OR 1.231, 95 % CI 1.081,1.401), NLR (OR 1.223, 95 % CI 1.064,1.405), PLR (OR 1.325, 95 % CI 1.086,1.617), PPN (OR 1.157, 95 % CI 1.031,1.298) and COPD, while a negative association was obtained between LMR and COPD (OR 0.794, 95 % CI 0.666,0.948) after covariate adjustments. When divided COPD patients into spirometry-based and questionnaire-based, only SII (OR 1.310, 95%CI 1.122,1.529), PLR (OR 1.669, 95%CI 1.272,2.191) and PPN (OR 1.218, 95%CI 1.050,1.412) significantly correlated with spirometry-based COPD, while only NLR (OR 1.303, 95%CI 1.055,1.609) and LMR (OR 0.524, 95%CI 0.406,0.677) significantly correlated with questionnaire-based COPD after covariate adjustments. ConclusionSignificant associations are observed between different inflammation indices and COPD. Heterogeneity exists between spirometry-based and questionnaire-based COPD patients. Future studies are needed to verify the results.

Recently Updated Role of Chitinase 3-like 1 on Various Cell Types as a Major Influencer of Chronic Inflammation.

Chitinase 3-like 1 (also known as CHI3L1 or YKL-40) is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but it is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce mammalian chitinases, such as CHI3L1, to protect the body from exogenous pathogens as well as hostile environments, and it was thought that it had a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pathophysiological role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we summarize the expression of CHI3L1 under chronic inflammatory conditions in various disorders and discuss the potential roles of CHI3L1 in those disorders on various cell types.

Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases.

Macrophages, the predominant immune cells in the lungs, play a pivotal role in maintaining the delicate balance of the pulmonary immune microenvironment. However, in chronic inflammatory lung diseases and lung cancer, macrophage phenotypes undergo distinct transitions, with M1-predominant macrophages promoting inflammatory damage and M2-predominant macrophages fostering cancer progression. Exosomes, as critical mediators of intercellular signaling and substance exchange, participate in pathological reshaping of macrophages during development of pulmonary inflammatory diseases and lung cancer. Specifically, in inflammatory lung diseases, exosomes promote the pro-inflammatory phenotype of macrophages, suppress the anti-inflammatory phenotype, and subsequently, exosomes released by reshaped macrophages further exacerbate inflammatory damage. In cancer, exosomes promote pro-tumor tumor-associated macrophages (TAMs); inhibit anti-tumor TAMs; and exosomes released by TAMs further enhance tumor proliferation, metastasis, and resistance to chemotherapy. Simultaneously, exosomes exhibit a dual role, holding the potential to transmit immune-modulating molecules and load therapeutic agents and offering prospects for restoring immune dysregulation in macrophages during chronic inflammatory lung diseases and lung cancer. In chronic inflammatory lung diseases, this is manifested by exosomes reshaping anti-inflammatory macrophages, inhibiting pro-inflammatory macrophages, and alleviating inflammatory damage post-reshaping. In lung cancer, exosomes reshape anti-tumor macrophages, inhibit pro-tumor macrophages, and reshaped macrophages secrete exosomes that suppress lung cancer development. Looking ahead, efficient and targeted exosome-based therapies may emerge as a promising direction for treatment of pulmonary diseases.

Positron emission tomography in artificial stone silicosis

Artificial stone (AS) silicosis has emerged as a specially aggressive form of silicosis that can lead to pulmonary fibrosis and respiratory failure. The utility of positron emission tomography combined with computed tomography (PET/CT), an essential tool in oncological diseases that shows increased metabolic activity in neoplastic cells, is being evaluated in inflammatory pulmonary diseases. There are few publications about its use in silicosis, almost always referred to isolated cases in the context of studying a possible neoplasm. We present four cases of AS silicosis that underwent PET/CT and discuss its possible usefulness in this entity.

Poly(malic acid)-budesonide nanoconjugates embedded in microparticles for lung administration.

To improve the therapeutic activity of inhaled glucocorticoids and reduce potential side effects, we designed a formulation combining the advantages of nanoparticles, which have an enhanced uptake by alveolar cells, allow targeted delivery and sustained drug release, as well as limited drug systemic passage, with those of microparticles, which display good alveolar deposition. Herein, a polymer-drug conjugate, poly(malic acid)-budesonide (PMAB), was first synthesized with either 11, 20, 33, or 43mol% budesonide (drug:polymer from 1:8 to 3:4), the drug creating hydrophobic domains. The obtained conjugates self-assemble into nanoconjugates in water, yielding excellent drug loading of up to 73 wt%, with 80-100nm diameters. In vitro assays showed that budesonide could be steadily released from the nanoconjugates, and the anti-inflammatory activity was preserved, as evidenced by reduced cytokine production in LPS-activated RAW 264.7 macrophages. Nanoconjugates were then embedded into microparticles through spray-drying with L-leucine, forming nano-embedded microparticles (NEMs). NEMs were produced with an aerodynamic diameter close to 1µm and a density below 0.1 g.cm-3, indicative of a high alveolar deposition. NEMs spray-dried with the less hydrophobic nanoconjugates, PMAB 1:4, were readily dissolved in simulated lung fluid and were chosen for in vivo experiments to study pharmacokinetics in healthy rats. As it was released in vivo from NEMs, sustained distribution of budesonide was obtained for 48 h in lung tissue, cells, and lining fluid. With high loading rates, modulable release kinetics, and low cytotoxicity, these nanoconjugates delivered by NEMs are promising for the more efficient treatment of pulmonary inflammatory diseases.

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration

This study investigated the anti-inflammatory and protective properties of SP-8356, a synthetic derivative of (1S)-(-)-verbenone, in a mouse model of LPS-induced acute lung injury (ALI). By targeting intracellular signaling pathways and inflammatory responses, SP-8356 demonstrated a potent ability to attenuate deleterious effects of proinflammatory stimuli. Specifically, SP-8356 effectively inhibited the activation of crucial signaling molecules such as NF-κB and Akt, and subsequently dampened the expression of inflammatory cytokines in various lung cellular components. Intervention with SP-8356 treatment also preserved the structural integrity of the epithelial and endothelial barriers. By reducing immune cell infiltration into inflamed lung tissue, SP-8356 exerted a broad protective effect against ALI. These findings position SP-8356 as a promising therapeutic candidate for pulmonary inflammatory diseases that cause ALI.

Occupational respiratory disorders in Iran: a review of prevalence and inducers.

The link between occupational respiratory diseases (ORD) and exposure to harmful factors that are present in the workplace has been well shown. Factors such as physical activity, age and duration of occupational exposure playing important roles in ORD severity, should be identified in the workplace, their effects on workers health should be studied, and ultimately, exposure to them must be minimized. We carried out a literature review by searching PubMed, Scopus, and Web of Science databases to retrieve studies published from 1999 until the end of April 2023 reporting the prevalence and inducers of ORD in Iran. In Iranian workers, several ORD such as interstitial lung disease, silicosis, occupational asthma, pulmonary inflammatory diseases, chronic obstructive pulmonary diseases, and lung cancers have been reported. It was indicated that ORD mainly occur due to repeated and prolonged exposure to noxious agents in the workplace. We also extracted the prevalence of ORD in different regions of Iran from the retrieved reports. Based on our literature review, the prevalence of ORD among Iranian workers highlights the importance of regular assessment of the risk of exposure to noxious agents in the workplace to develop measures for preventing potential adverse effects.

A remodeled ivermectin polycaprolactone-based nanoparticles for inhalation as a promising treatment of pulmonary inflammatory diseases

In recent years, ivermectin (IVM), an antiparasitic drug of low water solubility and poor oral bioavailability, has shown a profound effect on inflammatory mediators involved in diseases, such as acute lung injury, lung fibrosis, and COVID-19. In order to maximize drug bioavailability, polymeric nanoparticles can be delivered through nebulizers for pulmonary administration. The aim of this study was to prepare IVM-loaded polycaprolactone (PCL) nanoparticles (NPs) by solvent evaporation method. Box-Benkhen design (BBD) was used to optimize entrapment efficiency (Y1), percent drug release after 6 h (Y2), particle size (Y3), and zeta potential (Y4). A study was conducted examining the effects of three independent variables: PCL-IVM ratio (A), polyvinyl alcohol (PVA) concentration (B), and sonication time (C). The optimized formula was also compared to the oral IVM dispersion for lung deposition, in-vivo behavior, and pharmacokinetic parameters. The optimized IVM-PCL-NPs formulation was spherical in shape with entrapment efficiency (% EE) of 93.99 ± 0.96 %, about 62.71 ± 0.53 % released after 6 h, particle size of 100.07 ± 0.73 nm and zeta potential of -3.30 ± 0.23 mV. Comparing the optimized formulation to IVM-dispersion, the optimized formulation demonstrated greater bioavailability with greater area under the curve AUC0–t of 710.91 ± 15.22 μg .ml−1.h for lung and 637.97 ± 15.43 μg .ml−1.h for plasma. Based on the results, the optimized NPs accumulated better in lung tissues, exhibiting a twofold longer residence time (MRT 4.78 ± 0.55 h) than the IVM-dispersion (MRT 2.64 ± 0.64 h). The optimized nanoparticle formulation also achieved higher cmax (194.90 ± 5.01 μg/ml), and lower kel (0.21 ± 0.04 h−1) in lungs. Additionally, the level of inflammatory mediators was markedly reduced. To conclude, inhalable IVM-PCL-NPs formulation was suitable for the pulmonary delivery and may be one of the most promising approaches to increase IVM bioavailability for the successful treatment of a variety of lung diseases.

Rhinovirus protease cleavage of nucleoporins: perspective on implications for airway remodeling.

Human Rhinoviruses (RV) are a major cause of common colds and infections in early childhood and can lead to subsequent development of asthma via an as yet unknown mechanism. Asthma is a chronic inflammatory pulmonary disease characterized by significant airway remodeling. A key component of airway remodeling is the transdifferentiation of airway epithelial and fibroblast cells into cells with a more contractile phenotype. Interestingly, transforming growth factor-beta (TGF-β), a well characterized inducer of transdifferentiation, is significantly higher in airways of asthmatics compared to non-asthmatics. RV infection induces TGF-β signaling, at the same time nucleoporins (Nups), including Nup153, are cleaved by RV proteases disrupting nucleocytoplasmic transport. As Nup153 regulates nuclear export of SMAD2, a key intermediate in the TGF-β transdifferentiation pathway, its loss of function would result in nuclear retention of SMAD2 and dysregulated TGF-β signaling. We hypothesize that RV infection leads to increased nuclear SMAD2, resulting in sustained TGF-β induced gene expression, priming the airway for subsequent development of asthma. Our hypothesis brings together disparate studies on RV, asthma and Nup153 with the aim to prompt new research into the role of RV infection in development of asthma.

Роль тромбоцитов в патогенезе инфекционно-воспалительных заболеваний легких у детей (обзор литературы)

At present, a subject of scientific interest is the interaction of immune systems and hemostasis. New data on their synergistic effect in various diseases have been obtained in the last decade, which allowed to introduce the concept of "immunothrombosis". Inflammation and thrombosis factors are capable of mutual activation and enhancement. A special role in these processes belongs to platelets, which are classified as cellular effectors of antimicrobial host defence. These cells are among the first to react to the pathogen when it enters the bloodstream. Platelet activation ensures the direct eradication of pathogens, the immune cells involvement, the formation of primary thrombi to prevent the spread of infection, and the coagulation system process start. However, microthrombosis can become uncontrollable and irreversible during continued activation. Platelet dysfunction may be associated with a hyperergic inflammatory response of the body and a severe disease course. Concomitant endothelial dysfunction intensifies hypercoagulation and inflammatory response, increasing the risk of systemic inflammatory processes. The review examines current data on the platelet role in the pathogenesis of infectious and inflammatory pulmonary diseases in children, including destructive ones. KEYWORDS: hemostasis, platelets, immunity, inflammation, pneumonia, children, neutrophil extracellular traps, microthrombosis. FOR CITATION: Tolstova E.M., Besedina M.V., Zaytseva O.V., Kuzina S.R., Lokshina E.E., Haspekov D.V., Turishchev I.V., Belyaeva T.Yu. Platelets in the pathogenesis of infectious and inflammatory pulmonary diseases in children (literature review). Russian Journal of Woman and Child Health. 2024;7(1):58–63 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-9.

A bidirectional Mendelian randomization study investigating the relationship between genetically predicted systemic inflammatory regulators and chronic obstructive pulmonary disease

Research has shown a connection between inflammation and chronic obstructive pulmonary disease (COPD), however the relationship between inflammation mediators and COPD causation remains unknown. To investigate the causal relationship of mediators of inflammation and COPD, we conducted a two-sample Mendelian randomization (MR) study. In our study, we incorporated 41 regulators of inflammation from 8293 Finnish individuals from genome-wide association studies (GWASs) of COPD corresponding to GWAS summary data for 2115 cases and 454,233 healthy individuals in Europe. Our research validated that higher levels of interleukin 8 (IL-8) are related with a decrease occurrence of COPD (OR = 0.795, 95 % CI = 0.642–0.984, p = 0.035) but that elevated levels of interleukin 18(IL-18) and interleukin 2 (IL-2) may be connected to an amplified risk of COPD (OR = 1.247, 95 % CI = 1.011–1.538; p = 0.039; OR = 1.257, 95 % CI = 1.037–1.523, p = 0.020, respectively). According to our research, cytokines play a crucial role in the development of COPD, and further investigation is necessary to explore the potential of utilizing these cytokines as targets for treatment and prevention of COPD.

From Microbes to Immunity: A Comprehensive Review of Microbiome Modulation

The host environment and the native microbial population, or microbiota, make up the microbiome, which is changing how medical professionals see pathogens in connection to human disease and health. The discovery that the majority of bacteria in human bodies perform ecosystem-critical tasks that benefit the entire microbial host system is perhaps the most fundamental development. The microbiome is the broad term for the diverse and abundant population of bacteria found in the gastrointestinal system. This ecosystem contains billions of microbial cells, the majority of which are essential to the preservation of human health. Nutrient consumption, immunology, digestion, and metabolism have all been related to the microbiome. Scientific research has recently established a correlation between alterations in the microbiome and the development of cancer, obesity, inflammatory pulmonary disease, and cardiovascular complications. Epithelial-intestinal microbiome modifications have a substantial impact on the development of diseases and human health. Numerous factors contribute to these changes, such as underlying medical issues and lifestyle decisions. Depending on where in the body it occurs, dysbiosis increases an organism's susceptibility to various threats. Due to the inherent diversity of the human microbiota, these bacteria carry out specific metabolic tasks and play unique roles in each anatomical location. It follows that knowledge of the microbial makeup and activities of the human microbiome in connection to health and disease is essential.

Nicotinic acetylcholine receptor signaling maintains epithelial barrier integrity.

Disruption of epithelial barriers is a common disease manifestation in chronic degenerative diseases of the airways, lung, and intestine. Extensive human genetic studies have identified risk loci in such diseases, including in chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases. The genes associated with these loci have not fully been determined, and functional characterization of such genes requires extensive studies in model organisms. Here, we report the results of a screen in Drosophila melanogaster that allowed for rapid identification, validation, and prioritization of COPD risk genes that were selected based on risk loci identified in human genome-wide association studies (GWAS). Using intestinal barrier dysfunction in flies as a readout, our results validate the impact of candidate gene perturbations on epithelial barrier function in 56% of the cases, resulting in a prioritized target gene list. We further report the functional characterization in flies of one family of these genes, encoding for nicotinic acetylcholine receptor (nAchR) subunits. We find that nAchR signaling in enterocytes of the fly gut promotes epithelial barrier function and epithelial homeostasis by regulating the production of the peritrophic matrix. Our findings identify COPD-associated genes critical for epithelial barrier maintenance, and provide insight into the role of epithelial nAchR signaling for homeostasis.

Intercellular Communication in Airway Epithelial Cell Regeneration: Potential Roles of Connexins and Pannexins.

Connexins and pannexins are transmembrane proteins that can form direct (gap junctions) or indirect (connexons, pannexons) intercellular communication channels. By propagating ions, metabolites, sugars, nucleotides, miRNAs, and/or second messengers, they participate in a variety of physiological functions, such as tissue homeostasis and host defense. There is solid evidence supporting a role for intercellular signaling in various pulmonary inflammatory diseases where alteration of connexin/pannexin channel functional expression occurs, thus leading to abnormal intercellular communication pathways and contributing to pathophysiological aspects, such as innate immune defense and remodeling. The integrity of the airway epithelium, which is the first line of defense against invading microbes, is established and maintained by a repair mechanism that involves processes such as proliferation, migration, and differentiation. Here, we briefly summarize current knowledge on the contribution of connexins and pannexins to necessary processes of tissue repair and speculate on their possible involvement in the shaping of the airway epithelium integrity.

Unwinding circular RNA's role in inflammatory pulmonary diseases.

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.

Regulation of von Willebrand factor by ADAMTS13 ameliorates lipopolysaccharide-induced lung injury in mice.

The relationship between von Willebrand factor (VWF) and inflammation has attracted considerable attention in recent years. VWF, which is stored in the Weibel-Palade bodies (WPBs) of endothelial cells (ECs), is released from WPBs in response to inflammatory stimuli and is thought to contribute to inflammation by promoting leukocyte extravasation. In this study, lung injury model mice were produced by intratracheal injection with lipopolysaccharides. The severity of lung inflammation was evaluated in mice with different genotypes (wild-type, Vwf-/-, Adamts13-/-) and mice treated with drugs that inhibit VWF function. Lung inflammation was significantly ameliorated in Vwf-/- mice compared with wild-type mice. Furthermore, inflammation was significantly suppressed in wild-type mice treated with anti-VWF A1 antibody or recombinant human ADAMTS13 compared with the untreated control group. The underlying mechanism appears to be an increased VWF/ADAMTS13 ratio at the site of inflammation and the interaction between blood cell components, such as leukocytes and platelets, and the VWF A1 domain, which promotes leukocyte infiltration into the lung. This study suggested that ADAMTS13 protein and other VWF-targeting agents may be a novel therapeutic option for treatment of pulmonary inflammatory diseases.

Activating transcription factor 3: A potential therapeutic target for inflammatory pulmonary diseases.

Activating transcription factor 3 (ATF3) is a nuclear protein that is widely expressed in a variety of cells. It is a stress-inducible transcription gene and a member of the activating transcription factor/cAMP responsive element-binding protein (ATF/CREB) family. The comprehensive literature review was conducted by searching PubMed and Google Scholar. Search terms used were "ATF3", "ATF3 and (ALI or ARDS)", "ATF3 and COPD", "ATF3 and PF", and "ATF3 and Posttranslational modifications". Recent studies have shown that ATF3 plays a critical role in many inflammatory pulmonary diseases, including acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF). ATF3 participates in many signaling pathways and complex pathophysiological processes, such as inflammation, immunity, endoplasmic reticulum stress, and cell proliferation. However, the role of ATF3 in current studies is controversial, and there are reports showing that ATF3 plays different roles in different pulmonary diseases. In this review, we first summarized the structure, function, and mechanism of ATF3 in various inflammatory pulmonary diseases. The impact of ATF3 on disease pathogenesis and the clinical implications was particularly focused on, with an overall aim to identify new targets for treating inflammatory pulmonary diseases.

The regulatory effect of intermittent fasting on inflammasome activation in health and disease.

Intermittent fasting (IF), one of the most popular diets, can regulate inflammation and promote health; however, the detailed molecular mechanisms are not fully understood. The present review aims to provide an overview of recent preclinical and clinical studies that have examined the effect of IF on inflammasome signaling, and to discuss the translational gap between preclinical and clinical studies. Three databases (PubMed, Web of Science, and Embase) were searched to identify all relevant preclinical and clinical studies up to October 30, 2022. A total of 1544 studies were identified through the database searches, and 29 preclinical and 10 clinical studies were included. Twenty-three of the 29 preclinical studies reported that IF treatment could reduce inflammasome activation in neurological diseases, metabolic and cardiovascular diseases, immune and inflammatory diseases, gastrointestinal diseases, and pulmonary diseases, and 7 of the 10 clinical studies demonstrated reduced inflammasome activation after IF intervention in both healthy and obese participants. Among various IF regimens, time-restricted eating seemed to be the most effective one in terms of inflammasome regulation, and the efficacy of IF might increase over time. This review highlights the regulatory effect of IF on inflammasome activation in health and disease. Future studies using different IF regimens, in various populations, are needed in order to evaluate its potential to be used alone or as an adjunct therapy in humans to improve health and counteract diseases.