Gastroesophageal Reflux Disease in Idiopathic Pulmonary Fibrosis: Uncertainties and Controversies.

The mechanisms of idiopathic pulmonary fibrosis (IPF), a rare, devastating disease with a median survival of 3-5 years, are not fully understood. Gastroesophageal reflux disease (GERD) is a frequent comorbidity encountered in IPF. Hypothetically, GERD-associated microaspiration may lead to persistent inflammation impairing lung infrastructure, thereby possibly accelerating the progression of IPF. IPF may increase intrathoracic pressure, which can aggravate GERD and vice versa. On the basis of the possible beneficial effects of antireflux or antacid therapy on lung function, acute exacerbation, and survival, the recent international IPF guideline recommends antacid therapies for patients with IPF, regardless of symptomatic GERD. However, due to newer conflicting data, several national guidelines do not support this recommendation. Elucidation of these questions by further clinical and bench-to-bedside research may provide us with rational clinical diagnostic and therapeutic approaches concerning GERD in IPF. The present review aims to discuss the latest data on the controversial association of IPF and GERD.

Corilagin attenuates aerosol bleomycin-induced experimental lung injury.

Idiopathic pulmonary fibrosis (IPF) is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson's trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKKα, phosphorylated IKKα (p-IKKα), NF-κB P65, TNF-α and IL-1ß, and reduced I-κB expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p) more dramatically than by low dose (10 mg/kg i.p). Last, corilagin inhibits TGF-ß1 production and α-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-κB and TGF-ß1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis.

IDI1 inhibits the cGAS-Sting signaling pathway in hepatocellular carcinoma.

Metabolic reprogramming is one of the prominent features that distinguishes tumor cells from normal cells. The role of metabolic abnormalities in regulating innate immunity is poorly understood. In this study, we found that IDI1 is significantly upregulated in liver cancer. IDI1 has no significant effect on the growth or invasion of liver cancer cells but significantly promotes liver cancer development in mice. Through molecular mechanism studies, we found that IDI1 interacts with the important regulator of innate immunity cGAS and recruits the E3 ligase TRIM41 to promote cGAS ubiquitination and degradation, inhibiting the cGAS-Sting signaling pathway. IDI1 inhibits the phosphorylation of TBK1 and the downstream factor IRF3 as well as the expression of CCL5 and CXCL10. In summary, this study revealed the important role of the metabolic enzyme IDI1 in the regulation of innate immunity, suggesting that it may be a potential target for liver cancer treatment.

Expression of miR-320 and miR-204 in myocardial infarction and correlation with prognosis and degree of heart failure.

Myocardial infarction is a very dangerous cardiovascular disease with a high mortality rate under the modern developed medical technology. miRNA is a small molecule regulatory RNA discovered in recent years, which can play an important role in many cancers and other diseases. Medical data, machine learning and medical care strategies supporting the Internet of Things (IoMT) have certain applications in the treatment of myocardial infarction. However, the specific pathogenesis of myocardial infarction is still unclear. Therefore, this paper aimed to explore the expression of microRNA-320 and microRNA-204 in myocardial infarction and used the expression of microRNA-320 and microRNA-204 to predict the prognosis of patients with myocardial infarction. In order to discuss the expression of microRNA-320 and microRNA-204 in myocardial infarction in more detail. In this paper, 40 patients in the trial period were selected for clinical research, and 10 patients with normal cardiac function were selected in NHF group as control group. 10 patients with heart failure were selected as AMHF group. 10 patients with acute myocardial infarction were selected as AMNHF group. 10 patients with heart failure after old myocardial infarction were selected as OMHF group. AMHF group, AMNHF group and OMHF group were taken as the case group. This paper analyzed the difference of miR between different groups and determined that there were significant differences in the expression of miR-320 and miR-204 between different groups. Finally, the expression and prognosis of miR-320 and miR-204 in myocardial infarction were analyzed. The analysis results showed that the expression of microRNA-320 and microRNA-204 can inhibit the activity of myocardial cells. On the fifth day, the corresponding expression of microRNA-320 and microRNA-204 reduced the optical density of myocardial cells to 1.75 and 1.76, which was significantly lower than that on the first day. Moreover, excessive miR-320 expression and excessive miR-204 expression can increase the apoptosis rate of myocardial cells. The above results indicated that the high expression of microRNA-320 and microRNA-204 can be a bad prognostic factor in patients with myocardial infarction, showing that medical data, machine learning and medical care strategies supporting IoMT can play a role in the treatment of myocardial infarction. Therefore, it is urgent to understand the pathogenesis of heart failure after myocardial infarction and find new treatment schemes to improve the positive prognosis.

Type I and type II Helicobacter pylori infection status and their impact on gastrin and pepsinogen level in a gastric cancer prevalent area.

BACKGROUND: Type I Helicobacter pylori (H. pylori) infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis. However, its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated; it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17 (G-17) and pepsinogens (PGs) during clinical practice. AIM: To explore the prevalence of type I and type II H. pylori infection status and their impact on G-17 and PG levels in clinical practice. METHODS: Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined, and 523 patients were enrolled in this study. H. pylori infection was confirmed by both 13C-urea breath test and serological assay. Patients were divided into non-atrophic gastritis (NAG), non-atrophic gastritis with erosion (NAGE), chronic atrophic gastritis (CAG), peptic ulcers (PU) and gastric cancer (GC) groups. Their serological G-17, PG I and PG II values and PG I/PG II ratio were also measured. RESULTS: A total H. pylori infection rate of 3572 examined patients was 75.9%, the infection rate of 523 enrolled patients was 76.9%, among which type I H. pylori infection accounted for 72.4% (291/402) and type II was 27.6%; 88.4% of GC patients were H. pylori positive, and 84.2% of them were type I infection, only 11.6% of GC patients were H. pylori negative. Infection rates of type I H. pylori in NAG, NAGE, CAG, PU and GC groups were 67.9%, 62.7%, 79.7%, 77.6% and 84.2%, respectively. H. pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio. Both types of H. pylori induced higher G-17 level, but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG, NAGE and CAG groups over uninfected controls. Overall PG I levels showed no difference among all disease groups and in the presence or absence of H. pylori; in stratified analysis, its level was increased in GC and PU patients in H. pylori and type I H. pylori-positive groups. CONCLUSION: Type I H. pylori infection is the major form of infection in this geographic region, and a very low percentage (11.6%) of GC patients are not infected by H. pylori. Both types of H. pylori induce an increase in G-17 level, while type I H. pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease. The data provide insights into H. pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.

Insulin-Like Growth Factor-1 Signaling in Lung Development and Inflammatory Lung Diseases.

Insulin-like growth factor-1 (IGF-1) was firstly identified as a hormone that mediates the biological effects of growth hormone. Accumulating data have indicated the role of IGF-1 signaling pathway in lung development and diseases such as congenital disorders, cancers, inflammation, and fibrosis. IGF-1 signaling modulates the development and differentiation of many types of lung cells, including airway basal cells, club cells, alveolar epithelial cells, and fibroblasts. IGF-1 signaling deficiency results in alveolar hyperplasia in humans and disrupted lung architecture in animal models. The components of IGF-1 signaling pathways are potentiated as biomarkers as they are dysregulated locally or systemically in lung diseases, whereas data may be inconsistent or even paradoxical among different studies. The usage of IGF-1-based therapeutic agents urges for more researches in developmental disorders and inflammatory lung diseases, as the majority of current data are collected from limited number of animal experiments and are generally less exuberant than those in lung cancer. Elucidation of these questions by further bench-to-bedside researches may provide us with rational clinical diagnostic approaches and agents concerning IGF-1 signaling in lung diseases.

CREB1 and Smad3 mediate TGF­ß3­induced Smad7 expression in rat hepatic stellate cells.

Transforming growth factor (TGF)­ß3 has previously been reported to antagonize hepatic fibrosis in vivo and in vitro. The present study aimed to investigate the mechanism underlying the involvement of TGF­ß3 in hepatic fibrosis. Short hairpin (sh)RNA­cAMP-responsive element binding protein (CREB) 1 and small interfering (si)RNA­Smad3 were utilized to silence the expression of CREB1 and Smad3 in hepatic stellate cells (HSCs), whereas the vector pRSV­CREB1 was used to induce CREB1 overexpression in HSCs. Cells were treated with or without exogenous TGF­ß3 or TGF­ß1, and mRNA and protein expression levels were assessed using reverse transcription­quantitative polymerase chain reaction and western blot analysis. Untreated cells served as the control group. Exogenous TGF­ß3 increased Smad7 mRNA and protein expression levels in rat HSCs, and CREB1 and Smad3 appeared to be implicated in the mechanism of Smad7. CREB1 knockdown inhibited the TGF­ß3­induced upregulation of Smad7, whereas its overexpression potentiated the Smad7 upregulation in HSCs; conversely, CREB1 manipulations had no effect on Smad7 expression under basal conditions. In addition, TGF­ß3­induced Smad7 upregulation was blocked when the activity of p38, a kinase upstream of CREB1, was inhibited. Furthermore, silencing Smad3 resulted in decreased Smad7 expression under basal conditions and in TGF­ß3­stimulated cells. Notably, Smad7 expression appeared to also be induced by exogenous TGF­ß1, independent of CREB1. The present study demonstrated that TGF­ß3 increased Smad7 expression in HSCs, whereas CREB1 and Smad3 appeared to participate in the mechanism of induction. Smad3 is the key regulator whereas CREB­1 acts as a co­regulator. These results suggested that this mechanism may underlie the antagonizing effects of TGF­ß3 on hepatic fibrosis.