Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

Health Inequalities of STEMI Care Before Implementation of a New Regional Network: A Prefecture-Level Analysis of Social Determinants of Healthcare in Yunnan, China.

BACKGROUND: As one of the most serious types of coronary heart disease, ST-elevation myocardial infarction (STEMI) faces huge challenges in the equal management and care of patients due to its life-threatening and time-critical condition. Health inequalities such as sex and age differences in STEMI care have been reported from developed countries. However, limited outcomes have been investigated and the major drivers of inequality are still unclear, especially in under-developed areas. This study aimed to explore the major drivers of health inequalities in STEMI care before implementation of a new regional network in the south-west of China. METHODS: Prefecture-level data of STEMI patients before the implementation of a regional network were analysed retrospectively. Drivers of inequality were identified from six social determinants of health, namely area of residence, ethnicity, sex, age, education and occupation. Outcomes of STEMI care included timely presentation, reperfusion therapy, timely reperfusion therapy, heart failure, inpatient mortality, length of hospital stay, hospital costs, and various intervals of ischaemic time. RESULTS: A total of 376 STEMI patients in the research area before implementation of the STEMI network were included. Compared with urban residents, rural patients were significantly less likely to have timely presentation (odds ratio [OR]=0.47, 95% CI: 0.28-0.80, P=.004) and timely reperfusion therapy (OR=0.32, 95% CI: 0.14-0.70, P=.005). Rural residents were less likely to present to hospital promptly than urban residents (HR=0.65, 95% CI=0.52-0.82, P<.001). In the first 3 hours of percutaneous coronary intervention (PCI) reperfusion delay and first 6 hours of total ischaemic time, rural patients had a significantly lower probability to receive prompt PCI (hazard ratio [HR]=0.40, 95% CI: 0.29-0.54, P<.001) and reperfusion therapy (HR=0.37, 95% CI: 0.25-0.56, P<.001) compared to urban patients. CONCLUSION: Rural residents were a major vulnerable group before implementation of the regional STEMI network. No obvious inequalities in ethnicity, sex, age, education or occupation existed in STEMI care in Chuxiong Prefecture of China.

MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to luteolin by directly targeting HK1.

Luteolin is a flavonoid compound derived from Lonicera japonica Thunb, which has been reported to exert anticancer effects on different types of tumors. miRNAs are a kind of endogenous non-coding small RNAs, which involved in occurrence and development of multi cancer, including miR-34a. However, the relationship between miR-34a and luteolin's susceptibility to cancer cells still remains unclear. In this study, we explored the roles of miR-34a and the effects of luteolin on GC cells as well as the underlying mechanism of miR-34a in mediating the susceptibility of GC cell to luteolin. Retrospectively study revealed that miR-34a expression was downregulated in human primary GC tissues compared with non-tumor tissues and low miR-34a expression was associated with a significantly shorter overall survival and disease-free survival. MiR-34a overexpression could inhibit GC cells and induce G1 phase arrest via p53/p21 and MAPK /ERK pathways. Luteolin decreased viability of GC cells in a dose-dependent manner. Meanwhile, miR-34a was found to be markedly upregulated in GC cells induced by luteolin and decreased miR-34a level was found in the artificial luteolin-resistant GC cells. Upregulation of miR-34a in luteolin-resistant GC cell could enhance the sensibility of GC cells to luteolin. On the other hand, miR-34a inhibitor could partly counter the anticancer effect of luteolin. In a further assay, we also found that targeting miR-34a could mediate the susceptibility of mouse xenografts to luteolin. Subsequent study found that HK1 was a direct target of miR-34a and downregulated HK1 mRNA or protein levels were presented after miRNA-34a overexpression in GC cells. Moreover, HK1 protein levels was decreased after luteolin treatment and partly restored when co-treated with luteolin and miR-34a inhibitor. Downregulation of HK1 in luteolin-resistant GC cell could increase the cell's sensitivity to luteolin. Therefore, our findings firstly suggested that miR-34a could modulate the susceptibility of gastric cancer cell to luteolin via targeting HK1, potentially benefiting GC patients' treatment in the future.

Clinical Significance of miR-149 in the Survival of Patients with Laryngeal Squamous Cell Carcinoma.

MicroRNAs (miRNAs) play critical roles in the progression of laryngeal cancer (LC). In this study, we aimed to investigate whether miR-149 is associated with the prognosis of patients with LC. A total of 97 laryngeal squamous cell carcinoma patients who underwent tumor resection were included in our follow-up study. In vitro studies was performed in cancer cell line Hep-2 to explore the antitumor role of miR-149 in LC. We found that the expression of miR-149 was significantly lower in tumor tissues, compared with vocal cord polyp tissues (P < 0.05). Kaplan-Meier analysis revealed that miR-149 expression status is significantly associated with survival duration (log rank test, P < 0.05), and multivariate Cox regression analysis revealed that patients with low miR-149 expression had shorter survival times compared with patients with high miR-149 expression. In vitro studies revealed that the exogenous expression of miRNA-149 inhibits the proliferation of human Hep-2 cells and induces cell apoptosis. Our study suggests that miR-149 expression in laryngeal squamous cell carcinoma tissues is critically associated with the prognosis of patients, and the ectopic expression of miR-149 in Hep-2 cells inhibits proliferation and cell cycle progression.

Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces.

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm (101.32 ± 11.16 kPa), 2.6 ± 0.16 atm (263.44 ± 16.21 kPa), and 3.6 ± 0.16 atm (364.77 ± 16.21 kPa), respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

Role of regulatory T cell in clinical outcome of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a life-threatening disease worldwide. Regulatory T cells (Treg cells) were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4 + cells that express CD25 and transcription factor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI. METHODS: A clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University (Tianjin, China). Forty patients and 30 healthy controls were recruited from August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1, 4, 7, 14, and 21 days after TBI. Blood sample (1 ml) was withdrawn in the morning and processed within 2 h. RESULTS: There was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1 st day after TBI. Treg level was decreased on the 4 th day, climbed up on the 7 th day and peaked on 14 th day after TBI. Treg cells declined to the normal level on 21 th day after TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4 + mononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 + mononuclear cells in the first 14 days. CONCLUSIONS: The level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.

Dexamethasone exacerbates spatial acquisition deficits after traumatic brain injury in rats.

OBJECTIVES: Given after traumatic brain injury (TBI), Dexamethasone (DXM) reduces cerebral edema but impairs retrograde memory. This study was designed to test the hypothesis that administration of DXM to rats with TBI promotes learning deficits that are correlated with the morphological changes of hippocampal pyramidal neurons. METHODS: Adult male Wistar rats were subjected to fluid percussion injury (FPI), received DXM (5 and 10 mg/kg), and then trained for spatial acquisition. Brain sections were examined by H.E. and Golgi impregnation to quantitatively measure the morphological changes of hippocampal pyramidal neurons. RESULTS: The latency and path length were significantly higher in rats with FPI than those in control groups, particularly in rats receiving post-trauma high-dose DXM. At the same time, Golgi impregnation revealed a significant decrease in the number of apical and basal dendrites of pyramidal neurons of ipsilateral hippocampus in rats after injury, but the decrease was greatest of CA3 pyramidal neurons of ipsilateral hippocampus in injured rats that also received high-dose DXM. DISCUSSION: These findings indicate that the administration of high-dose DXM after TBI could worsen the dendritic atrophy of hippocampal CA3 pyramidal neurons and, as a result, exacerbate spatial acquisition deficits.