Qingfei xieding prescription ameliorates mitochondrial DNA-initiated inflammation in bleomycin-induced pulmonary fibrosis through activating autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingfei Xieding prescription was gradually refined and produced by Hangzhou Red Cross Hospital. The raw material includes Ephedra sinica Stapf, Morus alba L., Bombyx Batryticatus, Gypsum Fibrosum, Prunus armeniaca L. var. ansu Maxim., Houttuynia cordata Thunb. , Pueraria edulis Pamp. Paeonia L., Scutellaria baicalensis Georgi and Anemarrhena asphodeloides Bge. It is effective in clinical adjuvant treatment of patients with pulmonary diseases. AIM OF THE STUDY: To explore the efficacy and underlying mechanism of Qingfei Xieding (QF) in the treatment of bleomycin-induced mouse model. MATERIALS AND METHODS: TGF-ß induced fibrotic phenotype in vitro. Bleomycin injection induced lung tissue fibrosis mouse model in vivo. Flow cytometry was used to detect apoptosis, cellular ROS and lipid oxidation. Mitochondria substructure was observed by transmission electron microscopy. Autophagolysosome and nuclear entry of P65 were monitored by immunofluorescence. Quantitative real-time PCR was performed to detect the transcription of genes associated with mtDNA-cGAS-STING pathway and subsequent inflammatory signaling activation. RESULTS: TGF-ß induced the expression of α-SMA and Collagen I, inhibited cell viability in lung epithelial MLE-12 cells that was reversed by QF-containing serum. TGF-ß-mediated downregulation in autophagy, upregulation in lipid oxidation and ROS contents, and mitochondrial damage were rescued by QF-containing serum treatment, but CQ exposure, an autophagy inhibitor, prevented the protective role of QF. In addition to that, the decreased autophagolysosome in TGF-ß-exposed MLE-12 cells was reversed by QF and restored to low level in the combination treatment of QF and CQ. Mechanistically, QF-containing serum treatment significantly inhibited mtDNA-cGAS-STING pathway and subsequent inflammatory signaling in TGF-ß-challenged cells, which were abolished by CQ-mediated autophagy inhibition. In bleomycin-induced mouse model, QF ameliorated pulmonary fibrosis, reduced mortality, re-activated autophagy in lung tissues and restrained mtDNA-cGAS-STING inflammation pathway. However, the protective effects of QF in bleomycin-induced model mice were also abrogated by CQ. CONCLUSION: QF alleviated bleomycin-induced pulmonary fibrosis by activating autophagy, inhibiting mtDNA-cGAS-STING pathway-mediated inflammation. This research recognizes the protection role of QF on bleomycin-induced mouse model, and offers evidence for the potentiality of QF in clinical application for pulmonary fibrosis treatment.

Association between Serum 25-Hydroxyvitamin D and Abdominal Aortic Calcification: A Large Cross-Sectional Study.

In the American population, the relationship between the standardized serum 25-hydroxyvitamin D (25(OH)D) concentration and the risk of abdominal aortic calcification (AAC) is unclear. The purpose of our study was to investigate the relationship between serum 25(OH)D concentration and AAC risk. Participants from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2014 were analyzed cross sectionally. An analysis of the relationship between serum 25(OH)D concentration and incident AAC and severe AAC (SAAC) was based on the restricted cubic spline (RCS) and multivariable logistic regression model. In addition, generalized additive models with smooth functions were used to evaluate the relationship between serum 25(OH)D concentration and the degree of AAC. Finally, a subgroup analysis was conducted. There were a total of 3,040 individuals in our study. The serum 25(OH)D concentration was divided into quartiles (Q1: 9.37-50.5 nmol/L; Q2: 50.6-67.2 nmol/L; Q3: 67.3-85.8 nmol/L; and Q4: 85.9-318.0 nmol/L); the lowest quartile served as the reference group (Q1). After adjusting for known confounding variables, compared with the lowest quartile (Q1) of serum 25(OH)D concentration, the odds ratios with 95% confidence intervals for AAC and SAAC across the quartiles (Q2, Q3, and Q4) were (1.042 (0.812, 1.338), 0.863 (0.668, 1.115), and 1.022 (0.787, 1.327)) and (1.48 (0.87, 2.52), 1.70 (1.01, 2.92), and 2.13 (1.19, 3.86)), respectively. As shown by the RCS plot, the serum 25(OH)D concentration was associated with the risk of AAC/SAAC in a U-shaped pattern (P for nonlinearity <0.05). In addition, the degree of AAC decreased at first and then increased as the serum 25(OH)D concentration increased. In conclusion, a U-shaped relationship existed between serum 25(OH)D concentration and the risk of AAC and SAAC. Consequently, the risk of AAC and SAAC may be mitigated with regular monitoring and vitamin D supplementation.

Structural Characteristics of Polysaccharide GP2a in Gardenia jasminoides and Its Immunomodulatory Effect on Macrophages.

Here, we elucidated the structural characteristics of a polysaccharide isolated from Gardenia jasminoides Ellis (labeled as GP2a) and its immunomodulatory activity. GP2a is an acidic polysaccharide with a molecular weight of 44.8 kDa, mostly comprising galacturonic acid. Methylation analysis revealed 4-GalpA (74.8%) to be the major sugar residue in GP2a. Nuclear magnetic resonance analysis indicated that its main chain comprised →4)-α-D-GalpA-6-OMe-(1→4)-α-D-GalpA-(1→ and →4)-α-D-GalpA-6-OMe-(1→2)-α-L-Rhap-(1→, with galactan and arabinans linked to the C-4 position of →2)-α-L-Rhap-(1→ residue as branched chains. Furthermore, GP2a showed no obvious toxicity to macrophages (RAW 264.7) while enhancing cell viability in a dose- and time-dependent manner. Compared with untreated cells, nitric oxide production and secretion of cytokines, such as tumor necrosis factor-α, interferon-γ, interleukin (IL)-1ß, IL-6, and granulocyte macrophage colony stimulating factor, in GP2a-treated cells significantly increased after 48 h. At 300 µg/mL GP2a concentration, there was no significant difference in the cytokine levels in GP2a- and lipopolysaccharide-treated cells (the positive control). In summary, GP2a is a pectic polysaccharide with homogalacturonan and rhamnogalacturonan-I structural regions in the main chain. Based on its immunomodulatory effects in vitro, GP2a may have potential uses in functional food and medicine.

The effects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: A protocol for systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. There is a lack of evidence on the contribution of curcumin in the treatment of T2DM. We conducted a protocol for systematic review and meta-analysis to evaluate whether curcumin supplementation is effective and safe in T2DM patients. METHODS: The systematic review will follow the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P). We will obtain studies through PubMed, Cochrane Library, Embase, Web of Science, and Medline databases. In addition, we will also collect 4 databases of China: China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database. Eligible study conference abstracts and reference lists of manuscripts will be searched. The data collection and analysis will be conducted independently by 2 reviewers. Meta-analysis will be performed using Review Manager software, version 5.3 (Update Software Ltd, Oxford, Oxon, UK). RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: The findings of this systematic review may encourage supplementation of curcumin and its preparation specifically in T2DM patients. Nevertheless, the application of curcumin supplementation in clinical practice should be taken with individual's contributing factors.

A Chinese Traditional Therapy for Bleomycin-Induced Pulmonary Fibrosis in Mice.

Pulmonary fibrosis is a chronic and fatal disease of lung tissue with high incidence and mortality in the world. The exploration of effective treatment for pulmonary fibrosis remains an urgent challenge. In our study, Qingfei Xieding was investigated as a novel Chinese traditional patent medicine against pulmonary fibrosis. A pulmonary fibrosis mouse model was constructed by injecting with bleomycin sulfate. Following Qingfei Xieding administration, lung samples were collected to assess pulmonary phenotype changes by analyzing lung coefficient, wet/dry, and histopathologic section. Levels of nitric oxide (NO), hydroxyproline (HYP), malondialdehyde (MDA), and total antioxidant capacity were measured to evaluate the degree of oxidation. A single-cell gel electrophoresis (SCGE) assay was used to evaluate bleomycin-induced DNA damage. Western blotting and real-time quantitative PCR were performed to determine the abundance of inducible nitric oxide synthase (iNOS), connective tissue growth factor (CTGF), alpha smooth muscle actin (α-SMA), and fibronectin (FN). In the present study, Qingfei Xieding administration significantly attenuated bleomycin-induced pulmonary fibrosis in mice by reducing lung coefficient, wet/dry, NO, HYP, and MDA as well as the expression of iNOS, CTGF, α-SMA, FN, and DNA damage. The results indicated that Qingfei Xieding is effective to resist oxidative damage and histopathologic lesion, serving a protection role on bleomycin-induced pulmonary fibrosis.

Multivariable quantitative relation between cell viability and the exposure parameters of 9.33 GHz RF-EMP irradiation.

Qualitative analysis of the influence of a certain exposure parameter is commonly performed in bioelectromagnetic studies. However, since the exposure condition requires the control of multiple parameters, the diverse results caused by different combinations of these parameters requires further quantitative study of the multivariable (exposure parameters)-bioeffect relation to identify the rule describing bioelectromagnetic effects. The present work investigated the relation between cell viability and the three main exposure parameters (electric intensity (Es), pulse duration (τ) and pulse number (N)) of 9.33 GHz radiofrequency electromagnetic field (RF-EMP). Experiments showed that the inhibitory rate of cell viability (ρ) had a proportional relationship with Es and exponential relationship with N; the equation [Formula: see text] is proposed to quantitatively describe the relation between the cell viability and these three exposure parameters. This equation can be used to predict the significance of a 9.33 GHz RF-EMP-induced bioeffect under the conditions Es <106 kV/m, N < 100, and 300 < τ < 750 ns, under which nonthermal bioeffects dominate for 9.33GHz RF-EMP exposure.

A clinical retrospective analysis of factors associated with apathetic hyperthyroidism.

OBJECTIVE: Apathetic hyperthyroidism can be misdiagnosed or diagnosed late, and older patients are often susceptible to adverse effects of treatment for thyrotoxicosis. The aim of this study was to identify factors associated with apathetic hyperthyroidism. METHODS: We retrospectively examined serum calcium, phosphorus and bone-specific alkaline phosphatase (BAP) levels and thyroid-associated variables in 140 patients with apathetic hyperthyroidism, 456 patients with typical hyperthyroidism and 120 healthy subjects. RESULTS: Significant differences were identified with respect to age, serum calcium and corrected calcium, serum phosphorus, thyroid-stimulating hormone (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4)), the FT(3)/FT(4) ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, BAP and albumin among the typical and apathetic hyperthyroid and normal groups (all p < 0.001). Univariate logistic regression showed that age, serum calcium and corrected calcium, serum phosphorus, TSH, FT(4), FT(3)/FT(4) ratio, ALT, AST and BAP were significantly associated with apathetic hyperthyroidism, and multivariate logistic regression showed that age, corrected calcium, TSH, FT(4), FT(3)/FT(4) ratio, BAP and ALT were significantly associated with apathetic hyperthyroidism. CONCLUSION: Greater age, increased corrected calcium levels, decreased TSH levels, increased FT(4), a decreased FT(3)/FT(4) ratio, increased BAP levels and increased ALT levels may be significant factors for differentiating apathetic from typical hyperthyroidism. Coordinated assessment of these variables may aid in the accurate diagnosis and treatment of this disorder.

[Effects of plant species combination and water body nutrient level on the biomass accumulation and allocation of three kinds functional plants].

Four nutrient levels, i.e., 0.5 mg N x L(-1) and 0.1 mg P x L(-1) (I), 1.5 mg N x L(-1) and 0.3 mg P x L(-1) (II), 4.5 mg N x L(-1) and 0.9 mg P x L(-1) (III), and 13.5 mg N x L(-1) and 2.7 mg P x L(-1) (IV), were installed to study the effects of water body's nutrient level, plant species combination, and their interactions on the biomass accumulation and allocation of invasive floating species Eichhornia crassipes, native rooted leaf-floating species Jussiaea stipulacea, and submerged plant Vallisneria spiralis. The total, root, stem, and leaf biomass of E. crassipes and J. stipulacea, either in monoculture or in mixed-culture, increased with increasing water body's nutrient level, their total biomass in treatments III and IV being averagely 54.47% and 102.63% higher than that in treatments I and II, respectively. Under different plant species combination, the total, root, stem, and leaf biomass of V. spiralis showed a declining trend with the increase of nutrient level, and the total biomass of V. spiralis in treatments III and IV was averagely 45.88% lower than that in treatments I and II. The results of two-way ANOVA showed that water body's nutrient level had significant positive effects on the biomass of E. crassipes and J. stipulacea but negative effects on that of V. spiralis, and the effects of plant species combination varied with target plant species.