Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix.

Background: The etiological underpinnings of gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) remain elusive, coupled with a scarcity of effective therapeutic interventions for IPF. Angelicae sinensis radix (ASR, also named Danggui) is a Chinese herb with potential anti-fibrotic properties, that holds promise as a therapeutic agent for IPF. Objective: This study seeks to elucidate the causal interplay and potential mechanisms underlying the coexistence of GERD and IPF. Furthermore, it aims to investigate the regulatory effect of ASR on this complex relationship. Methods: A two-sample Mendelian randomization (TSMR) approach was employed to delineate the causal connection between gastroesophageal reflux disease and IPF, with Phennoscanner V2 employed to mitigate confounding factors. Utilizing single nucleotide polymorphism (SNPs) and publicly available microarray data, we analyzed potential targets and mechanisms related to IPF in GERD. Network pharmacology and molecular docking were employed to explore the targets and efficacy of ASR in treating GERD-related IPF. External datasets were subsequently utilized to identify potential diagnostic biomarkers for GERD-related IPF. Results: The IVW analysis demonstrated a positive causal relationship between GERD and IPF (IVW: OR = 1.002, 95%CI: 1.001, 1.003; p < 0.001). Twenty-five shared differentially expressed genes (DEGs) were identified. GO functional analysis revealed enrichment in neural, cellular, and brain development processes, concentrated in chromosomes and plasma membranes, with protein binding and activation involvement. KEGG analysis unveiled enrichment in proteoglycan, ERBB, and neuroactive ligand-receptor interaction pathways in cancer. Protein-protein interaction (PPI) analysis identified seven hub genes. Network pharmacology analysis demonstrated that 104 components of ASR targeted five hub genes (PDE4B, DRD2, ERBB4, ESR1, GRM8), with molecular docking confirming their excellent binding efficiency. GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF (ESR1: AUCGERD = 0.762, AUCIPF = 0.725; GRM8: AUCGERD = 0.717, AUCIPF = 0.908). GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF, validated in external datasets. Conclusion: This study establishes a causal link between GERD and IPF, identifying five key targets and two potential diagnostic biomarkers for GERD-related IPF. ASR exhibits intervention efficacy and favorable binding characteristics, positioning it as a promising candidate for treating GERD-related IPF. The potential regulatory mechanisms may involve cell responses to fibroblast growth factor stimulation and steroidal hormone-mediated signaling pathways.

Effects of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on cancer therapy-related cardiac dysfunction: a meta-analysis of randomized controlled trials.

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) may attenuate cancer therapy-related cardiac dysfunction (CTRCD). However, results of the previous studies were not consistent. We performed a meta-analysis to evaluate the influence of ACEI/ARB on CTRCD. Randomized controlled trials (RCTs) were obtained by searching of PubMed, Embase, and Cochrane's Library databases. A random-effect model was used to pool the results. Nine RCTs with 1095 cancer patients that underwent chemotherapy with anthracycline and/or trastuzumab were included. Using of ACEI/ARB significantly preserved left ventricular ejection fraction (LVEF, weighed mean difference = 4.24%, p = 0.002) compared with controls. Subgroup analyses showed that the benefits of ACEI/ARB on LVEF following chemotherapy were consistent and independent of study characteristics including study design, sample size, cancer type, chemotherapy protocols, preventative medications of ACEI or ARB, methods for LVEF measurement, and follow-up durations. The benefits on LVEF following chemotherapy were more remarkable in studies using ACEI and followed ≤ 12 months (p for subgroup difference = 0.04 and 0.02). Use of ACEI/ARB did not significantly reduce the risk of cardiotoxicity events (risk ratio [RR] = 0.63, p = 0.22) but increased the risk of hypotension in these patients (RR = 3.94, p = 0.008). These results indicated that using of ACEI/ARB may moderately attenuate CTRCD following chemotherapy with anthracycline and/or trastuzumab. Large-scale RCTs are needed to evaluate whether the benefits of ACEI/ARB on LVEF are clinically relevant.

Prognostic value of hyperuricemia in patients with acute coronary syndrome: A meta-analysis.

BACKGROUND: The prognostic significance of elevated circulating uric acid level in patients with acute coronary syndrome (ACS) is conflicting. This meta-analysis aimed to assess the prognostic value of hyperuricemia in patients with ACS. METHODS: A comprehensive literature search was performed in Pubmed, Embase, VIP, CNKI and WanFang databases up to 16 June 2018. All observational studies that investigated the prognostic value of hyperuricemia in ACS patients were selected. Outcome of interests was major adverse cardiovascular events (MACEs), all-cause mortality or cardiovascular mortality. RESULTS: A total of nine studies enrolling 8776 ACS patients were included and analysed. ACS patients with hyperuricemia had an increased risk of MACEs (risk ratio [RR]: 1.86; 95% confidence intervals [CI]: 1.47-2.35), all-cause mortality (RR 1.86; 95% CI: 1.49-2.32) and cardiovascular mortality (RR: 1.74; 95% CI: 1.36-2.22) after adjustment for the conventional risk factors. Stratified analysis showed that the prognostic significance of hyperuricemia was consistently observed in each subgroups. CONCLUSIONS: This meta-analysis suggests that hyperuricemia independently predicts MACEs and death in ACS patients. Determination of uric acid level has potential to improve risk stratification of adverse outcomes in ACS patients.