Ferroptosis Mediates Pulmonary Fibrosis: Implications for the Effect of Astragalus and Panax notoginseng Decoction.

Objective: To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods: First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor ß, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results: APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.

Targeting iron-metabolism:a potential therapeutic strategy for pulmonary fibrosis.

Iron homeostasisis is integral to normal physiological and biochemical processes of lungs. The maintenance of iron homeostasis involves the process of intake, storage and output, dependening on iron-regulated protein/iron response element system to operate tightly metabolism-related genes, including TFR1, DMT1, Fth, and FPN. Dysregulation of iron can lead to iron overload, which increases the virulence of microbial colonisers and the occurrence of oxidative stress, causing alveolar epithelial cells to undergo necrosis and apoptosis, and form extracellular matrix. Accumulated iron drive iron-dependent ferroptosis to exacerbated pulmonary fibrosis. Notably, the iron chelator deferoxamine and the lipophilic antioxidant ferritin-1 have been shown to attenuate ferroptosis and inhibit lipid peroxidation in pulmonary fibrosis. The paper summarises the regulatory mechanisms of dysregulated iron metabolism and ferroptosis in the development of pulmonary fibrosis. Targeting iron metabolism may be a potential therapeutic strategy for the prevention and treatment of pulmonary fibrosis.

Astragalus polysaccharide protects experimental colitis through an aryl hydrocarbon receptor-dependent autophagy mechanism.

BACKGROUND AND PURPOSE: Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR-dependent autophagy. EXPERIMENTAL APPROACH: The symptoms of dextran sulfate sodium (DSS)-induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild-type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS-induced AhRs and autophagic Becn1 was investigated using a dual-luciferase reporter system and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction assay. Caco-2 cells were used to investigate inflammatory responses and AhR-dependent autophagy. KEY RESULTS: APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS. CONCLUSIONS AND IMPLICATIONS: APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.

Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis.

BACKGROUND: To systematically analyze the value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial cancer, so as to provide evidence-based medical evidence for the selection of serum tumor markers in the early screening of endometrial cancer. METHODS: We comprehensively searched relevant literature in the Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, VIP, WanFang, and CBM from the date of establishment to November 31, 2021. Quality assessment of diagnostic accuracy studies 2 was applied to evaluate the quality of the included literature. We used Stata 16.0 to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and plot summary receiver operating characteristic curve, as well as to assess diagnostic accuracy using the area under the curve (AUC). RESULTS: A total of 25 studies, including 1980 patients and 2345 controls, were included in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 were 0.58 (95% CI 0.52-0.63), 0.95 (95% CI 0.92-0.97), 11.57 (95% CI 6.88-19.48), 0.45 (95% CI 0.39-0.51), 25.92 (95% CI 14.84-45.26), and 0.80 (95% CI 0.76-0.83), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of CA125 were 0.41 (95% CI 0.34-0.49), 0.91 (95% CI 0.85-0.95), 4.55 (95% CI 2.73-7.58), 0.65 (95% CI 0.57-0.74), 7.03 (95% CI 3.92-12.62), and 0.68 (95% CI 0.64-0.72), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 + CA125 were 0.67 (95% CI 0.60-0.73), 0.92 (95% CI 0.87-0.95), 8.59 (95% CI 5.32-13.86), 0.36 (95% CI 0.30-0.44), 23.80 (95% CI 13.86-40.86), and 0.85 (95% CI 0.82-0.88), respectively. CONCLUSION: This Meta-analysis found that HE4 alone or in combination with CA125 showed better diagnostic efficacy than CA125, regardless of clinical stage and pathological type. HE4 + CA125 had slightly higher diagnostic efficiency than HE4, but did not show significant advantages. While the studies were heterogeneous, the credibility of the findings needs to be further confirmed by more homogeneous, prospective, and large sample size studies.

Tang-Ping-San Decoction Remodel Intestinal Flora and Barrier to Ameliorate Type 2 Diabetes Mellitus in Rodent Model.

Purpose: Type 2 diabetes mellitus (T2DM) is a complex genetic disease associated with genetic and environmental factors. Previous studies have shown that changes in the gut microbiota may affect the development of host metabolic diseases and promote the progression of T2DM. Tang-ping-san (TPS) decoction can effectively treat T2DM. However, its specific mechanisms must be evaluated. Patients and Methods: In the present study, we established an animal model of T2DM using a high­fat diet (HFD) with intraperitoneal injection streptozotocin injection. Results: The therapeutic effect of TPS decoction on T2DM in mice was initially evaluated. TPS decoction was found to improve hyperglycemia, hyperlipidemia, insulin resistance, and pathological liver, pancreatic, and colon changes. Moreover, it reduced the pro-inflammatory cytokine levels. Based on 16SrRNA sequencing, TPS decoction reduced the Firmicutes/Bacteroidetes ratio at the phylum level. At the genus level, it increased the relative abundances of Akkermansia, Muribaculaceae, and the Eubacterium coprostanoligenes group and decreased the relative abundance of Fusobacterium, Escherichia coli, Dubosiella, and Helicobacter. Conclusion: TPS decoction improves T2DM and liver function and reduces the risk of hyperglycemia, hyperlipidemia, insulin resistance, pathological organ changes, and inflammatory reactions. The mechanism of TPS decoction in T2DM can be correlated with the reversal of gut microbiota dysfunction and repair of the intestinal mucosal barrier.

[Influence Factors and Sensitivity of Ozone Formation in Langfang in the Summer].

The diurnal variations in ozone concentrations in the summer were studied using the temperature, wind speed and direction, total cloud cover, and solar radiation intensity data collected in Langfang, China. The ratio of volatile organic compounds to nitrogen oxides (VOCs/NOx) and the EKMA curve were studied to analyze the sensitivity of ozone formation. The results showed that:① The ozone generation rate and ozone concentrations were positively correlated with the solar radiation intensity with Pearson correlation coefficients of 0.61 and 0.48, respectively. Both the ozone generation rate and the solar radiation intensity reached their peak at about 12:00, while the ozone concentration reached its peak at about 16:00, which lagged behind the peak of the solar radiation intensity by 4 h. ② The correlation coefficient between the ozone generation rate and the temperature was 0.44, between the ozone concentration and temperature was 0.68. The ozone generation rate and ozone concentrations were inversely correlated with total cloud cover with correlation coefficients of -0.24 and -0.45, respectively. ③ The ozone concentrations in Langfang were high when the winds were from the west, south, or southeast. ④ The ozone concentrations in Langfang were more sensitive to VOCs than to NOx; thus, they can be reduced efficiently by controlling the VOCs emissions.

[Safety and efficacy of firebird drug-eluting stent combination tirofiban in patients with acute coronary syndrome].

OBJECTIVE: To evaluate the safety and efficacy of Firebird drug-eluting stent (DES) combining Tirofiban and Cypher DES combining Tirofiban in patients with acute coronary syndrome (ACS). METHODS: 323 ACS patients were divided into 2 general conditions-matched groups: Firebird group (n = 161) undergoing Firebird DES implantation and Tirofiban intravenous injection 10 microg x kg(-1) within 3 minutes followed by Tirofiban 0.15 microg x kg(-1) x min(-1) intravenous maintenance infusion with micro pump for 36 hours, and Cypher group (n = 162) undergoing Cypher DES implantation and Tirofiban. The safety was observed instantly and 36 h after the implantation. The patients were followed up for 30 d. Some patients in the Firebird group underwent coronary angiography and intravascular ultrasound because of angina and part of target vessels underwent revascularization. RESULTS: There were no significant differences between the 2 groups in ejection fraction target coronary lesion type, blood platelet count, HB and HCT before treatment. The success rates of operation were both 100% in these 2 groups. No complication occurred in both groups. There were not significant differences in the blood platelet count, hemoglobin, hematocrit, acute stent thrombosis rate (1.2% vs 1.2%), acute myocardial infarction rate (1.3% vs 1.3%), target vessel revascularization rate (0.6% vs 1.3%), and rehospitalization rate (1.3% vs 0.7%) (all P > 0.05). 30 d no in-stent restenosis was found by angiographic and intravascular ultrasound follow-up in the Firebird group. CONCLUSION: Firebird DES combining Tirofiban and Cypher DES combining Tirofiban are both safe and effective in treating ACS.

[The experimental study on changes of endothelial nitric oxide synthase and plasminogen activator inhibitor-1 protein in the canine atrial fibrillation model].

OBJECTIVE: To evaluate the changes in the expressions of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) and the alterations of nitric oxide (NO) concentration in atrial endocardium in atrial fibrillation (AF) in order to investigate the mechanisms that contribute to thrombosis. METHODS: In canine AF was produced with rapid atrial pacing at 400 bpm for 6 weeks, whereas the controls had no atrial pacing. NO production was measured by NO-specific microelectrode. The expression of endocardial eNOS and PAI-1 protein were determined by Western blot analysis and immunohistochemical Staining. Plasma levels of PAI-1 were analysed by Enzyme-linked immunoadsorbent assay. RESULTS: Left atrial NO concentration was decreased in AF than that in controls [(23.4 +/- 5.8)nmol/L vs (63.8 +/- 16.1)nmol/L, P < 0.01]. Endocardial eNOS expression was also significantly decreased (855 +/- 217 vs 2320 +/- 694, P < 0.05), whereas the expression of the PAI-1 was increased (3164 +/- 827 vs 1371 +/- 352, P < 0.01). Neither NO concentration, nor PAI-1, eNOS expression were altered in the right atria at the same time. A significant increase for plasma levels of PAI-1 was also detected in AF group. No correlation was found between eNOS and PAI-1 protein expression (r = 0.217, P > 0.05). CONCLUSION: In the canine model AF was associated with a marked decrease in endocardial NOS expression and NO concentration and with an increase in PAI-1 expression in the left atrium, which may contribute to the thrombosis in AF.