Systematic identification of the interventional mechanism of Qingfei Xiaoyan Wan (QFXYW) in treatment of the cytokine storm in acute lung injury using transcriptomics-based system pharmacological analyses.

CONTEXT: Acute lung injury (ALI) is a complex, severe inflammation disease with high mortality, and there is no specific and effective treatment for ALI. Qingfei Xiaoyan Wan (QFXYW) has been widely used to treat lung-related diseases for centuries. OBJECTIVE: This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice. MATERIALS AND METHODS: BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways. RESULTS: QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 105/mL to (4.01 ± 0.11) × 105/mL, accompanied by the neutrophil from (1.41 ± 0.19) × 105/mL to (0.77 ± 0.10) × 105/mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway. CONCLUSIONS: This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

Mind Your Heart: Exploring Feasibility, Acceptability, and Preliminary Effects of Phone-Delivered Mindfulness Training on Medication Adherence in Outpatients With Chronic Heart Failure.

BACKGROUND: Mindfulness training (MT) may promote medication adherence in outpatients with heart failure. OBJECTIVE: The aims of this study were to determine the feasibility and acceptability of MT (primary outcomes) and explore effects on medication adherence, functional capacity, cognitive function, depression, and mindfulness skills (secondary outcomes). METHODS: In this pre/post-design study, participants received a 30-minute phone-delivered MT session weekly for 8 weeks. RESULTS: We enrolled 33 outpatients (32% women; 69.7 White; mean age, 60.3 years). Retention was 100%, and session attendance was 91%. Overall, participants (97%) rated MT as enjoyable. Objectively assessed ( P < .05) adherence decreased post intervention, whereas improvements were noted in functional capacity ( P = .05), mindfulness ( P < .05), and cognitive function (reaching significance for Flanker scores). CONCLUSIONS: Phone-delivered MT was feasible and acceptable. Whereas no improvements were noted in medication adherence and depression, cognitive function, functional capacity, and mindfulness levels increased post intervention, suggesting MT may have beneficial effects in outpatients with heart failure.

Integration of transcriptomics and system pharmacology to reveal the therapeutic mechanism underlying Qingfei Xiaoyan Wan to treat allergic asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a chronic inflammatory disease, characterized by airway inflammation, hyperresponsiveness, and bronchial smooth muscle contraction. Qingfei Xiaoyan Wan (QFXYW), a traditional Chinese formula, has been shown to exert anti-asthma effects and immune response in multiple diseases. AIM OF THIS STUDY: In this study, we evaluated the therapeutic mechanism of QFXYW in the suppression of allergic asthma by integrating of transcriptomics and system pharmacology. MATERIALS AND METHODS: BALB/c mice were sensitized with ovalbumin (OVA) to establish the allergic asthma model, and its success was confirmed with behavioral observations. Lung histopathological analysis, inflammatory pathology scores, transcription factors were used to evaluate the effects of QFXYW on allergic asthma. The therapeutic mechanism of QFXYW in treating allergic asthma through integrated transcriptomics and system pharmacology was then determined: hub genes were screened out by topological analysis and functional enrichment analysis were performed to identify key signaling pathway. Subsequently, quantitative RP-PCR and protein array were performed to detect the mRNA of hub genes and to predict the key pathway in OVA-induced allergic asthma, respectively. RESULTS: Our results demonstrated that QFXYW could significantly attenuate inflammatory cell infiltration, mucus secretion, and epithelial damage. The transcriptomics analysis found the six hub genes with the highest values- CXCL10, CXCL2, CXCL1, IL-6, CCL-5, and CCL-4 were screened out. Functional enrichment analysis showed that the differentially expressed genes (DEGs) were mainly enriched in the inflammatory response and cytokine signaling pathway. Moreover, the quantitative RT-PCR verification experiment found the CXCL2 and CXCL1 were significantly suppressed after treatment with QFXYW. The results of protein array showed that QFXYW inhibited the multi-cytokines of OVA-induced allergic asthma via cytokine signaling pathway. CONCLUSIONS: QFXYW may have mediated OVA-induced allergic asthma mainly through the hub genes CXCL2, CXCL1, and the cytokine signaling pathway. This finding will offer a novel strategy to explore effective and safe mechanism of Traditional Chinese Medicine (TCM) formula to treat allergic asthma.

Gardenia fructus antidepressant formula for depression in diabetes patients: A systematic review and meta-analysis.

INTRODUCTION: Diabetes is closely related with depression. Gardenia fructus antidepressant formula (GFAF) is a Chinese herbal medicine that may be beneficial for depression in diabetic patients. This study aimed to evaluate the efficacy and safety of GFAF for depression in diabetes patients. METHODS: Randomized controlled trials (RCTs) were included. The patients were diagnosed as having diabetes mellitus with depression. The experimental interventions included GFAF alone or combined with another active treatment. The control interventions included no treatment, placebo or another active treatment. The primary outcome was reduction in the Hamilton Depression Scale (HAMD) scores. Secondary outcomes included reduction in the Self-rating Depression Scale (SDS) scores, response rate, adverse events, etc. PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan fang database and Chinese Science and Technology Periodicals database (VIP) were searched from inception to May 2019 for potentially eligible studies. The meta-analysis was performed using RevMan 5.3 software. RESULTS: We identified 12 eligible RCTs including 822 diabetes patients with depression. Results of meta-analysis showed that the HAMD score was significantly reduced following GFAF treatment compared with no antidepressant treatment (SMD: -2.53, 95% CI: -4.80 to -0.27, P = 0.03). Another meta-analysis indicated that patients taking GFAF alone had lower HAMD scores compared with selective serotonin reuptake inhibitors (SSRI) treatment alone (SMD: -0.62, 95% CI: -1.07 to -0.18, P = 0.006). The HAMD scores in the GFAF plus SSRI treatment group were significantly decreased compared with the SSRI treatment group (SMD: -0.37, 95% CI: -0.69 to -0.06, P = 0.02). The same pattern of change was identified with the SDS scores. CONCLUSION: GFAF may be considered an alternative treatment for depression in patients with diabetes. However, more large-scale and well-designed RCTs are warranted.

Associations of Vitamin D Intake and Sleep Quality With Cognitive Dysfunction in Older Adults With Heart Failure.

BACKGROUND: Low vitamin D intake and poor sleep quality are independently associated with cognitive dysfunction in healthy older adults. However, the relationships among vitamin D intake, sleep quality, and cognitive dysfunction are unknown in older adults with heart failure (HF). PURPOSE: The aim of this study was to determine the relationships of vitamin D intake and sleep quality with cognitive dysfunction in older adults with HF. METHODS: A total of 160 older adults with HF completed the Mini-Mental State Examination to assess cognitive function. Vitamin D deficiency was defined as less than 15 mcg/day of average intake determined using a 3-day food diary and use of dietary supplements. Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI). Hierarchical regressions and mediation analysis were used for data analysis. RESULTS: Thirty-four patients (21.2%) had severe cognitive dysfunction (total Mini-Mental State Examination score ≤ 19), 88 (55%) had vitamin D deficiency, and 120 (75%) reported poor sleep quality (total PSQI score > 5). Increased daily vitamin D intake (ß = 0.305, P < .001) and poorer sleep quality indicated by the total PSQI score (ß = -0.312, P < .001) were associated with cognitive function. Vitamin D deficiency was associated with poor sleep quality (odds ratio, 2.22; P = .033). In mediation analysis, the relationship between vitamin D deficiency and cognitive function was mediated by sleep quality among older adults with HF. CONCLUSIONS: Both vitamin D deficiency and poor sleep quality are associated with cognitive dysfunction in older adults with HF. Interventions should be tested to target patients with poor sleep quality to improve cognitive function, particularly in those with vitamin D deficiency.

Vitamin D supplements reduce depressive symptoms and cardiac events in heart failure patients with moderate to severe depressive symptoms.

BACKGROUND: Depressive symptoms and vitamin D deficiency predict cardiac events in heart failure patients, but whether vitamin D supplements are associated with depressive symptoms and cardiac events in heart failure patients remains unknown. PURPOSE: The purpose of this study was to compare the association of vitamin D supplement use with depressive symptoms and cardiac events in heart failure patients with mild or moderate to severe depressive symptoms. METHODS: A total of 177 heart failure patients with depressive symptoms (Patient Health Questionnaire-9 score ≥5) completed a three-day food diary to determine dietary vitamin D deficiency. Patients were split into four groups by dietary vitamin D adequacy versus deficiency and vitamin D supplement use versus non-use. The Patient Health Questionnaire-9 was used to reassess depressive symptoms at six months. Data on cardiac events for up to one year and vitamin D supplement use were obtained from patient interview and medical record review. Hierarchical linear and Cox regressions were used for data analysis. RESULTS: Sixty-six patients (37.3%) had dietary vitamin D deficiency and 80 (45.2%) used vitamin D supplements. In patients with moderate to severe depressive symptoms, the group with dietary vitamin D deficiency and no supplements had the highest Patient Health Questionnaire-9 score at six months (ß=0.542, p<0.001) and shortest cardiac event-free survival ( p<0.001) among the four groups, the group with dietary vitamin D deficiency and no supplements didn't have the highest Patient Health Questionnaire-9 score at six months and shortest cardiac event-free survival in patients with mild depressive symptoms. CONCLUSIONS: Vitamin D supplements predicted lower depressive symptoms and reduced cardiac events for patients with moderate to severe depressive symptoms. Vitamin D deficiency was associated with higher risk of shorter cardiac event-free survival in heart failure patients regardless of vitamin D supplementation.