Pulmonary arterial hypertension (PAH) is a high mortality progressive pulmonary vascular disease that can lead to right heart failure. The use of clinical drugs for the treatment of PAH is limited to a great extent because of its single target and high price. Flavonoids are widely distributed in nature, and have been found in fruits, vegetables, and traditional Chinese medicine. They have diverse biological activities and various pharmacological effects such as antitumor, antioxidation, and anti-inflammatory. This review summarizes the progress in pharmacodynamics and mechanism of flavonoids in the treatment of PAH in recent years, in order to provide some theoretical references for relevant researchers.

Completing an ultramarathon leads to an immediate postrace surge of erythropoietin (EPO). Patients with chronic liver disease may have high plasma EPO concentrations. This study aims to explore whether plasma EPO concentrations vary between hepatitis B virus carrier (HBVc) and non-HBVc runners during long distance running. Blood samples were collected from 8 HBVc and 18 non-HBVc runners at 3 different time points: 1 week before, immediately following, and then 24 h after the 100-km ultramarathon race. Samples were analyzed for plasma EPO levels. EPO concentration had a statistically significant rise immediately after the race (8.7 [7.1–11.9] mU·mL⁻¹ to 23.7 [14.8–37.2] mU·mL⁻¹, P < 0.001) and maintained the high levels 24 h after the race finished (16.7 [11.5–21.0] mU·mL⁻¹, P < 0.001) in all participants. The mean of EPO concentration was 8.9 (5.7–13.2) mU·mL⁻¹ in HBVc runners and was 8.7 (7.7–11.2) mU·mL⁻¹ in non-HBVc runners in the prerace. In HBVc runners, plasma EPO levels were no different at baseline (P = 0.657) and increased in the same fashion in response to ultramarathon compared with non-HBVc runners. Plasma EPO levels between the two groups were not statistically different at any time point. Prolonged endurance exercise led to a significant increase in EPO. A comparable increase in EPO levels was observed in HBVc and non-HBVc runners during and 24 h after 100-km ultramarathon. However, a small sample size might have affected the ability to detect a difference if it does exist.

When irisin and adropin were discovered, it was popularly hoped that they would become therapies for metabolic disorders that threaten global health. However, contradictory results have been reported in the subsequent period. Irisin, induced by exercise or cold exposure, is believed to be a myokine that causes the browning of adipose tissue thus increasing energy expenditure. Adropin is thought to be beneficial for health by regulating blood flow, capillary density, and playing an active role in glucose and insulin homeostasis. However, there were no experimental studies investigating the simultaneous effect of exercise and cold exposure in humans. The purpose of this study was to investigate irisin and adropin responses in young healthy individuals performing aerobic exercise in different environmental temperatures. Twenty-seven young, healthy individuals participated in this study. Participants performed 40 min of aerobic running exercise in environmental temperatures of 0°C, 12°C, and 24°C. Venous blood samples were taken pre- and post-exercise. Irisin and adropin levels were analyzed using an enzyme-linked immunosorbent assay. The principal findings showed that while serum irisin concentrations significantly increased after aerobic exercise was performed at an environmental temperature of 0°C, there was no significant difference between pre- and post-exercise recordings for physical activity performed at 12°C and 24°C. Adropin concentrations, however, remained unchanged between pre- and post-exercise at 0°C, 12°C, and 24°C. Interestingly, the exercise at 0°C caused an increase in adropin (12.5%), but this amount was not enough to be a statistically significant result. The findings of this study suggest that aerobic exercise in a cold environment causes greater irisin release. However, the combined effect of exercise and cold exposure may not be enough to statistically increase adropin level.

Acute kidney injury (AKI) in community-acquired septic patients is often associated with relatively high mortality rate. However, the appropriate timing for continuous renal replacement therapy (CRRT) initiation remains controversial. In the present study, we retrospectively analyzed 123 community-acquired septic patients with AKI admitted to the medical intensive care unit (ICU). The baseline patient characteristics and renal function parameters were compared between survivors and non-survivors. Then, we used the Cox proportional hazard analysis to identify the risk factors for ICU mortality. Moreover, we employed the area under the receiver operating characteristic curve analysis to determine the cutoff time for CRRT initiation. Finally, we used the cutoff time to separate the patients into early (treatment initiated earlier than the cutoff time) and late (treatment initiated later than the cutoff time) CRRT groups and performed the Kaplan–Meier survival analysis to assess the overall mortalities. At the time of ICU release, the mortality rate of the 123 patients was 48.8% (n = 60). We identified several baseline characteristics and renal function parameters that were significantly different between the survivors and the non-survivors. All of them were also identified as the risk factors for community-acquired sepsis. Importantly, the cutoff time point to distinguish the early and late CRRT initiation groups was determined to be 16 h after AKI onset. Based on such grouping, the mortality rate was significantly lower in the early CRRT initiation group at 30, 60 and 90 days. Our data suggest that initiating CRRT within 16 h may help improve the mortality rate of community-acquired septic patients.

Epithelial–mesenchymal transition (EMT) is associated with malignant tumors. In a previous study, we found that KLHL23 is a tumor suppressor gene that inhibits EMT and cancer dissemination. However, the correlation between its expression and cancer progression in urothelial carcinoma (UC) remains unknown. This study showed that the deficiency of KLHL23 in the invasive leading cancer cells is important for improving cell migration in UC. Currently, little is known about the underlying mechanisms of KLHL23-mediated cytoskeleton remodeling in the metastatic leading cells of tumors. Our findings showed that silencing of KLHL23 promotes cell migration in UC by regulating the translocation of focal adhesion proteins. Lack of KLHL23 causes abnormal formation of lamellipodia and increases the EMT phenotype and migration. Wound healing assay revealed that KLHL23 potentiates the actin bundles and intracellular focal adhesion protein formation in the invasive leading cells. Knockdown of KLHL23 abolishes the formation of actin stress fibers and translocalizes vinculin to the perimembrane, which enhances the mobility of cancer cells. To elucidate the mechanism, we found that during migration, KLHL23 appears in the leading cells in large numbers and binds to the actin stress fibers. A large amount of vinculin accumulated at both ends of the KLHL23/actin fibers, indicating an increase in cell anchorage. Thus, KLHL23 might play a critical role in enhancing actin fibers and promoting focal adhesion complex formation in the invasive leading cells. Analysis of the overall survival revealed that low KLHL23 is associated with poor survival in patients with bladder UC, indicating its clinical significance. We hypothesize that KLHL23 is involved in the formation of actin stress fibers and focal adhesion complexes in the invasive leading cells and may be associated with EMT progression and prognosis in UC patients.

Two known coumarins, scopoletin (SP) and umbelliferone (UB), were isolated from Cortex Mori (CM). Their structures were elucidated by various spectroscopic analyses. Then, their effects on rat glomerular mesangial cells (RGMCs, HBZY-1) proliferation, hypertrophy, extracellular matrix (ECM) proliferation, expression of fibronectin, transforming growth factor-beta (TGF-β), and connective tissue growth factor (CTGF) induced by high glucose were studied in vitro model of diabetic glomerulosclerosis. The results show that, CM, SP, and UB can inhibit the RGMCs proliferation to attenuate the ECM proliferation and cell hypertrophy, reduced the accumulation of ECM protein fibronectin, and lowered the expression of the key fibrosis factor TGF-β and CTGF to inhibit the kidney fibrosis and thereby improved diabetic glomerulosclerosis. The two coumarins show great potentialities on treating diabetic glomerulosclerosis, but the animal experiment and mechanism is strongly needed for further proof.

This study investigated the effect of listening to self-music therapy training (SMT) music, which was specially developed using musical expectancy violations, on improving brain concentration and activation. It was performed with a sample of 12 adults. Electroencephalograms (EEG) were obtained and analyzed after allowing the participants to listen to SMT music. An EEG device with eight channels was used to measure the brain waves. The changes in the EEGs were recorded when listening to SMT music in three states (stable, basic, and stimulated) after attaching the electrodes to the prefrontal cortex (Fp1 and Fp2), and the frontal (F3 and F4), temporal (T3 and T4), and parietal lobes (P3 and P4) according to the International 10/20 system. The EEG data were analyzed to determine the m-β wave appearance rate and absolute total power (ATP) for the three conditions, and a t-test was performed. The results showed that the rate of m-β wave appearance was higher in the stimulated and basic states than in the stable state (Fp1, Fp2, F4, T3, T4, P3, and P4) and higher in the stimulated state than in the basic state (Fp1, Fp2, T3, T4, and P4). The ATP was lower in the basic state than in the stable state (Fp2, F3, F4, and T3), but the ATP in the stimulated state was higher than in the basic or stable state in all areas excluding the left and right parietal lobes (Fp1, Fp2, F3, F4, T3, and T4). These results demonstrated that listening to SMT music by normal adults could increase brain concentration and activation.