Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway.

Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.

Crocin Alleviates Intracerebral Hemorrhage-Induced Neuronal Ferroptosis by Facilitating Nrf2 Nuclear Translocation.

Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe2+ concentration and the expression of GPX4, FTH1, and SLC7A11. Mechanistically, crocin treatment increased the expression and nuclear translocation of Nrf2. Our data suggest that crocin alleviates intracerebral hemorrhage-induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation.

Correlation between Traditional Chinese Medicine Syndromes and Type 2 Myocardial Infarction in Critically Ill Patients with Pulmonary Disease.

Background: Treatment based on syndrome differentiation under the traditional Chinese medicine (TCM) framework has been shown to be helpful in patients with coronary artery disease. We hypothesized that syndrome types could predict the risk of type 2 myocardial infarction (T2MI) caused by imbalance between myocardial oxygen supply and demand in critically ill patients with pulmonary disease. Methods: This retrospective study included consecutive critically ill patients with pulmonary disease admitted to the ICU at Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from January 1, 2017, to July 1, 2019. Diagnosis of T2MI was based on the fourth universal definition of myocardial infarction. Risk factors associated with T2MI were identified using multivariate regression analysis. Results: A total of 244 patients were included in the study: 78 who developed T2MI and the remaining 166 who did not develop T2MI during hospitalization. The incidence of phlegm syndrome and deficiency syndrome was 61.9% and 38.1%, respectively. In comparison with the patients with phlegm syndrome, the incidence of T2MI in patients with deficiency syndrome is significantly higher (40.9% vs. 26.5%, P=0.019). In multivariate logistic regression, T2MI was independently associated with the baseline troponin level (OR 12.682, 95% CI 1.397∼115.121; P=0.024), hemoglobin < 55 g/L (OR 12.76, 95% CI 2.359∼69.021; P=0.003), mechanical ventilation (OR 2.244, 95% CI 1.029∼4.892; P=0.042), and TCM deficiency syndrome (OR 2.214, 95% CI 1.032∼4.749; P=0.041). After adjusting for confounding factors in Cox regression models, the hazard ratio (95% confidence interval) of qi deficiency syndrome groups was 1.183 (95% CI 1.053∼3.123, P=0.032). Conclusions: Patients with deficiency syndrome are at high risk of T2MI, especially those combined with qi deficiency syndrome.

Hypoxia/reoxygenation-induced upregulation of miRNA-542-5p aggravated cardiomyocyte injury by repressing autophagy.

MicroRNAs (miRNAs) and autophagy exert an important role in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. The current study aimed to explore the role of miRNA and autophagy in H/R-induced cardiomyocyte injury. Cardiomyocyte H9c2 was exposed to H/R to simulate H/R injury in vitro. The differentially expressed miRNAs were identified using quantitative RT-PCR (qPCR). Lactate dehydrogenase (LDH) activity was assayed to assess H/R injury. The role of miRNA and autophagy in regulating the viability and cell apoptosis was evaluated using cell counting kit-8 (CCK-8) assay, flow cytometry (FCM), and western blot. The autophagy activation was assessed through testing the number of light chain 3 (LC3) puncta and LC3-II expression using western blot and immunofluorescence analysis. In the present study, we found that the miR-542-5p expression and the autophagy activation were significantly increased in H9c2 cells after H/R injury. Functionally, forced expression of miR-542-5p further aggravated H/R injury in H9c2 cells, whereas miR-542-5p inhibition alleviated H/R injury as measured by the cell viability, LDH activity and cell apoptosis. miR-542-5p repressed autophagy activation, whereas miR-542-5p inhibition facilitated autophagy activation in H9c2 cells exposed to H/R as measured by the LC3 puncta number, LC3II, and p62 protein level. Especially, autophagy inhibition by specific inhibitor partially lessened the role of miR-542-5p inhibitor in alleviating H/R injury. Finally, the autophagy-related 7 (ATG7) was identified as a novel target gene of miR-542-5p in H9c2 cells. The current data suggest that miR-542-5p/autophagy pathway might be a potential target for the treatment of H/R-related heart diseases.

Analysis of risk factors for cervical lymph node metastasis of papillary thyroid microcarcinoma: a study of 268 patients.

BACKGROUND: To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients. METHODS: We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression. RESULTS: Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006). CONCLUSION: Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.

Serum iron levels are an independent predictor of in-hospital mortality of critically ill patients: a retrospective, single-institution study.

OBJECTIVE: This study aimed to examine the relationship between serum iron levels and in-hospital mortality in critically ill patients. METHODS: We retrospectively studied 250 critically ill patients who received treatment at the intensive care unit between June 2015 and May 2017. Blood chemistry and hepatic and renal function were measured. Kaplan-Meier survival curves were plotted according to serum iron levels. Correlations between serum iron levels and other variables were analyzed. RESULTS: A total of 165 (66.0%) patients had abnormally low serum iron levels (<10.6 µmol/L). Patients who died during hospitalization had markedly higher Acute Physiology and Chronic Health Evaluation II scores and significantly lower serum iron levels compared with those who survived. Cumulative survival was significantly lower in patients with low serum iron levels than in those with normal serum iron levels in subgroup analysis of older patients (n = 192). Multivariate regression analysis showed that, after adjusting for relevant factors, low serum iron levels remained an independent risk for in-hospital mortality (odds ratio 2.014; 95% confidence interval 1.089, 3.725). CONCLUSIONS: Low serum iron levels are present in a significant proportion of critically ill patients and are associated with higher in-hospital mortality, particularly in older patients.

Dynamic Change of Red Cell Distribution Width Levels in Prediction of Hospital Mortality in Chinese Elderly Patients with Septic Shock.

BACKGROUND: The normal range of red cell distribution width (RDW) level is <15%. Several studies have indicated that a high RDW level was associated with mortality in critically ill patients, and the patients with a high RDW level need increased focus in clinical practice. In view of the difficulty in defining the specific value of high RDW level, the key is to focus on the patient with the level beyond the normal upper limit. This study aimed to determine whether dynamic change of RDW levels, rather than the level itself, is predictive of death in elderly patients with septic shock when RDW level is beyond 15%. METHODS: Between September 2013 and September 2015, the elderly septic shock patients with RDW level beyond 15% were enrolled in this study. The RDW levels were measured at enrollment (day 1), and days 4 and 7 after enrollment. Sequential Organ Failure Assessment (SOFA) scores were recorded simultaneously. RESULTS: A total of 45 patients, including 32 males and 13 females, were included in the final analysis. Based on their hospital outcomes, these patients were divided into the survivor group (n = 26) and the nonsurvivor group (n = 19). There were no significant differences in age, gender, body mass index, initial level of RDW, Acute Physiology and Chronic Health Evaluation II scores, and SOFA scores between survivors and nonsurvivors. At days 4 and 7 measurement, both RDW level (median [interquartile range]: day 4: 15.8 [2.0]% vs. 16.7 [2.0]%, P= 0.011; and day 7: 15.6 [1.8]% vs. 17.7 [2.5]%, P= 0.001) and SOFA scores (day 4: 7.0 [4.0] vs. 16.0 [5.0], P< 0.001, day 7: 5.5 [4.0] vs. 17.0 [5.0], P< 0.001) were significantly lower in survivors than those in nonsurvivors. Dynamic changes of RDW and SOFA scores in survivor group were significantly different from those in nonsurvivor group (all P< 0.05). Continuous increase in RDW level was observed in 10 of the 13 nonsurvivors, but only in 3 of the 26 survivors. The level of RDW7 and dynamic changes significantly correlated with their counterparts of SOFA scores (all P< 0.05), whereas the levels of RDW1 and RDW4 had no significant correlation with their counterparts of SOFA scores (all P> 0.05). CONCLUSIONS: Continuous increase in RDW level, rather than the level of RDW itself, was more useful in predicting hospital death in elderly patients with septic shock when the level of RDW was >15%. The dynamic changes of RDW were highly correlated with the SOFA score in the patients.