Synergistic effect of paeoniflorin combined with luteolin in alleviating Lipopolysaccharides-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is an acute multifactorial infectious disease caused by trauma, pneumonia, shock and sepsis. Paeoniae Radix Rubra (Paeonia lactiflora Pall. or Paeonia veitchii Lynch, Chishao in Chinese, CS) and Salviae Miltiorrhizae Radix et Rhizoma (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese, DS) are common traditional Chinese medicines (TCMs). CS-DS herb pair has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, appearing in a variety of prescriptions. However, it is still unclear for the effect and active ingredients of the herb pair on ALI. AIM OF THE STUDY: The study investigated the effect and active ingredients of CS-DS herb pair and demonstrated the synergistic effect and mechanisms of the active ingredients. MATERIALS AND METHODS: Lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage cells and BALB/c mice were used to establish an ALI model to investigate the effect of CS-DS herb pair on ALI. Network pharmacology and molecular docking were used to analyze the active ingredients and potential mechanisms of the herb pair. The synergistic effects and mechanisms of active ingredients on ALI were validated by in vitro and in vivo experiments. RESULTS: CS-DS herb pair had a synergistic effect on LPS-induced ALI. Based on the network pharmacology, the compounds paeoniflorin and luteolin were screened. Both paeoniflorin and luteolin had good affinity for NF-κB and MAPK by molecular docking. LPS stimulation of RAW264.7 cells resulted in a significant increase in ROS, NO, TNF-α, IL-6 and IL-1ß, while the paeoniflorin combined with luteolin significantly reduced their expressions. In the LPS-induced ALI model, the combination also reduced the expression of inflammatory factors and oxidative stress levels. Furthermore, LPS activated the NF-κB and MAPK signaling pathways, whereas the combination decreased the expression of proteins in both pathways. CONCLUSION: CS-DS herb pair alleviated LPS-induced ALI with the active ingredients paeoniflorin and luteolin, which suppressed inflammation and oxidative stress via regulation of NF-κB and MAPK signaling pathways.

Preoperative MRI Classification May Not Predict Symptom Relief after Uterine Artery Embolization in Patients with Adenomyosis.

OBJECTIVE: To investigate the association between magnetic resonance imaging (MRI) classification and symptom relief after uterine artery embolization (UAE) in patients with adenomyosis. METHODS: Totally, 73 patients with symptomatic adenomyosis who underwent UAE were retrospectively analyzed. Preoperative MRI classification was defined as: type I, high signal on both T2-weighted images (T2WI) and T1-weighted images (T1WI); type III, high signal only on T2WI, and type II, high signal on neither T1WI nor T2WI. Dysmenorrhea was measured with the visual-analog scales and the degree of menorrhagia was measured according to the number of sanitary pads used in one menstrual cycle. Dysmenorrhea and menorrhagia were measured before UAE and 12 months after UAE. RESULTS: The number of the type I, II, III cases was 23, 37, and 13, respectively. The baseline characteristics of the three groups exhibited no significant difference. The alleviation rates of dysmenorrhea among type I, II, III cases were 73.9%, 89.2%, and 84.6%, respectively (P=0.455). The alleviation rates of menorrhagia for type I, II, III were 69.6%, 78.4%, and 92.3%, respectively (P=0.714). CONCLUSION: Pre-procedure MRI classification and symptom relief after UAE exhibited no significant association. UAE has a favorable mid-term control on dysmenorrhea and menorrhagia among patients with adenomyosis. Preoperative MRI classification might not indicate symptom relief. More research is needed before changing clinical practice.

Liraglutide protects palmitate-induced INS-1 cell injury by enhancing autophagy mediated via FoxO1.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and a progressive loss in mass and function of pancreatic ß-cells. In T2DM, lipotoxicity leads to ß-cells dysfunction and decreases its number. Autophagy serves a crucial role in maintaining the normal islet architecture and the function of ß-cells. Moreover, glucagon-like peptide-1 (GLP-1) and its analogs have beneficial roles in pancreatic ß-cells. However, the protective effects of GLP-1 agents on palmitate (PA)-induced pancreatic ß-cells and their underlying mechanisms are not fully elucidated. Forkhead box O1 (FoxO1) can prevent pancreatic ß-cells from apoptosis. Whether GLP-1 protects against PA-induced ß-cells injury via FoxO1 remains unknown. The present study exposed INS-1 cells to PA to establish a T2DM injury model. Cell viability was evaluated using a Cell Counting Kit-8 assay, and apoptosis was determined via western blotting. Furthermore, autophagy was examined using western blotting, immunofluorescence and transmission electron microscopy. Silencing FoxO1 was used to inhibit the activities of FoxO1. The results suggested that the GLP-1 analog liraglutide enhanced the cell viability, inhibited the protein expression of cleaved caspase-3 and increased the expression levels of microtubule-associated protein 1 light chain3 (LC3) II/I, and FoxO1 in INS-1 cells. The autophagy inhibitor chloroquine inhibited the protective effects of liraglutide on INS-1 cells. Silencing of FoxO1 decreased the expression levels of LC3-II and attenuated the protection of liraglutide on the viability of INS-1 cells. In conclusion, the results indicated that liraglutide ameliorated the PA-induced islet ß-cells injury via the upregulation of autophagy-mediated by FoxO1.

Predisposing factors for predicting the therapeutic response of adenomyosis after uterine artery embolization: serum CA125 levels and accompanying endometriosis.

PURPOSE: We aimed to identify predisposing factors that could help predict the therapeutic response of adenomyosis after uterine artery embolization (UAE). METHODS: This was a retrospective, single-center study of patients admitted to the hospital for adenomyosis between 2013 and 2015. Sixty-eight patients with adenomyosis who underwent UAE with tris-acryl gelatin microspheres were divided into two groups based on their therapeutic response (complete or incomplete necrosis of lesions), and pre- and postprocedural pelvic magnetic resonance imaging (MRI) data. Patients were followed up for 12 months after UAE. Improvements in dysmenorrhea and menorrhagia were evaluated based on the symptom relief criteria. Improvement rates in both groups were analyzed and compared. Multivariate logistic regression analysis was used to identify the predisposing factors from retrospectively gathered baseline data that might affect the therapeutic response, including MRI features, clinical symptoms, biochemical index, and accompanying diseases of adenomyosis. Then, a prognostic model was established, and the receiver operating characteristic (ROC) curve of identified factors was drawn to determine their predictive value. RESULTS: Following UAE, 46 patients (67.6%) showed complete necrosis, while 22 patients (32.4%) showed incomplete necrosis. At 12-month follow-up, dysmenorrhea symptom improvement was seen in 94.7% of complete necrosis and 50% of incomplete necrosis group (P < 0.001); menorrhagia symptom improvement was seen in 96.2% of complete necrosis and 57.1% of incomplete necrosis groups (P = 0.004). Multivariate logistic regression analysis determined serum cancer antigen 125 (CA125) levels (odds ratio [OR], 1.006; 95% confidence interval [CI], 1.002-1.010; P = 0.005) and accompanying endometriosis (OR, 6.869; 95% CI, 1.881-25.016; P = 0.004) as predisposing factors. The areas under the ROC curve of CA125, endometriosis, and these two indicators combined were 0.785, 0.708, and 0.845, which corresponded to sensitivities of 95.5%, 66.7%, and 68.2% and specificities of 52.2%, 80.0%, and 87.0% at optimal cutoff values, respectively. CONCLUSION: Symptom relief of dysmenorrhea and menorrhagia for patients with complete necrosis was significantly better than that for patients with incomplete necrosis. Serum CA125 levels and accompanying endometriosis can effectively distinguish complete necrosis from incomplete necrosis.

Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and remains a major cause of preventable blindness among adults at working age. DR involves an abnormal pathology of major retinal cells, including retinal pigment epithelium, microaneurysms, inter-retinal oedema, haemorrhage, exudates (hard exudates) and intraocular neovascularization. Hyperglycemia is the driving force for the development of diabetic retinopathy. The exact cause of diabetic nephropathy is unknown, but various postulated mechanisms are: hyperglycemia, advanced glycosylation products, activation of cytokines. In this review article, we have discussed a number of diabetes-induced metabolites such as glucose, advanced glycation end products, protein kinase C and oxidative stress and other related factors that are implicated in the pathophysiology of the DR. An understanding of the biochemical and molecular changes especially early in the DR may lead to new and effective therapies towards prevention and amelioration of DR.

Role of the calpain on the development of diabetes mellitus and its chronic complications.

Diabetes mellitus (DM) is associated with acute and chronic complications that cause major morbidity and significant mortality. Calpains, a family of Ca(2+)-dependent cytosolic cysteine proteases, can modulate their substrates' structure and function through limited proteolytic activity. Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic function. However, alterations in calcium homeostasis lead to pathologic activation of calpain in diabetes mellitus. Since not much is known on the relationship between calpain and diabetes mellitus, this review outlines the contribution of calpain to chronic complications of diabetes mellitus, such as diabetic cardiomyopathy, diabetic nephropathy and diabetic retinopathy.