Adenosine is involved in a range of physiological and pathological effects through membrane-bound receptors linked to G proteins. There are four subtypes of adenosine receptors, described as A1AR, A2AAR, A2BAR, and A3AR, which are the center of cAMP signal pathway-based drug development. Several types of agonists, partial agonists or antagonists, and allosteric substances have been synthesized from these receptors as new therapeutic drug candidates. Research efforts surrounding A1AR and A2AAR are perhaps the most enticing because of their concentration and affinity; however, as a consequence of distressing conditions, both A2BAR and A3AR levels might accumulate. This review focuses on the biological features of each adenosine receptor as the basis of ligand production and describes clinical studies of adenosine receptor-associated pharmaceuticals in human diseases.

CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the deposition of a pathological extracellular matrix (ECM). Additionally, many omics studies confirmed that aberrant cellular senescence-associated mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, alveolar endothelial cells, fibroblasts, and macrophages). Here, we reviewed the role of the CTGF in IPF lung cells to mediate anomalous senescence-related metabolic mechanisms that support the fibrotic environment in IPF.

The hedgehog (Hh) pathway is a sophisticated conserved cell signaling pathway that plays an essential role in controlling cell specification and proliferation, survival factors, and tissue patterning formation during embryonic development. Hh signal activity does not entirely disappear after development and may be reactivated in adulthood within tissue-injury-associated diseases, including idiopathic pulmonary fibrosis (IPF). The dysregulation of Hh-associated activating transcription factors, genomic abnormalities, and microenvironments is a co-factor that induces the initiation and progression of IPF.

Idiopathic pulmonary fibrosis (IPF), one of the most common fibrosing interstitial lung diseases (ILD), is a chronic-age-related respiratory disease that rises from repeated micro-injury of the alveolar epithelium. Environmental influences, intrinsic factors, genetic and epigenetic risk factors that lead to chronic inflammation might be implicated in the development of IPF. The exact triggers that initiate the fibrotic response in IPF remain enigmatic, but there is now increasing evidence supporting the role of chronic exposure of viral infection. During viral infection, activation of the NLRP3 inflammasome by integrating multiple cellular and molecular signaling implicates robust inflammation, fibroblast proliferation, activation of myofibroblast, matrix deposition, and aberrant epithelial-mesenchymal function. Overall, the crosstalk of the NLRP3 inflammasome and viruses can activate immune responses and inflammasome-associated molecules in the development, progression, and exacerbation of IPF.

Background: The combination of gemcitabine (GEM) and paclitaxel (PTX) was appealing for clinical exploration due to different mechanisms of action and partially non-overlapping toxicities. Purpose: The aim of this study was to elucidate a potential effect of this combination on the proliferation of two non-small cell lung cancer (NSCLC) cell lines, A549 and H520. Materials and methods: Cell lines were treated with GEM and PTX for 48 hours to evaluate the half maximal inhibitory concentration (IC50). To determine the combination index (CI), cell lines were exposed to GEM and PTX, in a constant ratio of IC50, by various combination treatments. GEM`s effect on tubulin was assessed by western blotting and immunofluorescent staining. GEM was combined with nanoparticle albumin-bound-paclitaxel (NP) in evaluating tumor growth inhibition. Results: The IC50 of GEM and PTX in A549 and H520 were 6.6 nM and 46.1 nM, and 1.35 nM and 7.59 nM, respectively. Among the sequences explored (GEM→PTX, PTX→GEM, and GEM plus PTX simultaneously [GEM+PTX]), GEM→PTX produced a mean CI <1 in both cell lines. Western blotting and immunofluorescent staining revealed the intention expressions of acetylated tubulin protein and enhancement of tubulin polymerization within GEM→PTX group. A combination order GEM→NP also worked synergistically to suppress tumor growth. Conclusion: The GEM→PTX sequence may represent a promising candidate regimen for the treatment of NSLCL.

A sedentary lifestyle and an unhealthy diet increase the risk of obesity. People with obesity experience adipocyte hypertrophy and hyperplasia, which increases the production of proinflammatory cytokines, thereby increasing the risk of morbidity and mortality. Lifestyle modification using non-pharmacological approaches such as physical exercise prevents increased morbidity through its anti-inflammatory effects. The purpose of this study was to examine the effects of different types of exercise on decreased proinflammatory cytokines in young adult females with obesity. A total of 36 female students from Malang City aged 21.86 ± 1.39 years with body mass index (BMI) of 30.93 ± 3.51 kg/m2 were recruited and followed three different types of exercise interventions: moderate-intensity endurance training (MIET), moderate-intensity resistance training (MIRT), and moderate-intensity combined training (MICT). The exercise was performed at a frequency of 3x/week for 4 weeks. Statistical analysis was performed using the Statistical Package for Social Science (SPSS) version 21.0, using the paired sample t-test. The results revealed that serum IL-6 and TNF-α levels were significantly decreased between pre-training and post-training in the three types of exercise (MIET, MIRT, and MICT) (p ≤ 0.001). The percentage change in IL-6 levels from pre-training in CTRL was (0.76 ± 13.58%), in MIET was (−82.79 ± 8.73%), in MIRT was (−58.30 ± 18.05%), in MICT was (−96.91 ± 2.39%), and (p ≤ 0.001). There was a percentage change in TNF-α levels from pre-training in CTRL (6.46 ± 12.13%), MIET (−53.11 ± 20.02%), MIRT (−42.59 ± 21.64%), and MICT (−73.41 ± 14.50%), and (p ≤ 0.001). All three types of exercise consistently reduced proinflammatory cytokines such as serum levels of IL-6 and TNF-α.

The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibrosis has implicated immunoreceptor tyrosine-based motif-bearing CTLRs as being involved, either directly or indirectly, in the pathogenesis of fibrosing ILD.

Genetic information is not transmitted solely by DNA but by the epigenetics process. Epigenetics describes molecular missing link pathways that could bridge the gap between the genetic background and environmental risk factors that contribute to the pathogenesis of pulmonary fibrosis. Specific epigenetic patterns, especially DNA methylation, histone modifications, long non-coding, and microRNA (miRNAs), affect the endophenotypes underlying the development of idiopathic pulmonary fibrosis (IPF). Among all the epigenetic marks, DNA methylation modifications have been the most widely studied in IPF. This review summarizes the current knowledge concerning DNA methylation changes in pulmonary fibrosis and demonstrates a promising novel epigenetics-based precision medicine.