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.

Rac1 Signaling in Amygdala Astrocytes Regulates Fear Memory Acquisition and Retrieval.

The importance of astrocytes in behavior control is increasingly appreciated, but little is known about the effects of their dynamic activity in regulating learning and memory. In the present study, we constructed AAVs of photoactivatable and photoinactivatable Ras-related C3 botulinum toxin substrate 1 (Rac1) under the mGFAP promoter, which enabled the manipulation of Rac1 activity in astrocytes by optical stimulation in free-moving mice. We found that both up-regulation and down-regulation of astrocytic Rac1 activity in the basolateral amygdala (BLA) attenuated memory acquisition in a fear conditioning mouse model. Meanwhile, neuronal activation in the BLA induced by memory acquisition was inhibited under both the up- and down-regulation of astrocytic Rac1 activity during training. In terms of the impact on fear memory retrieval, we found both up- and down-regulation of BLA astrocytic Rac1 activity impaired memory retrieval of fear conditioning and memory retrieval-induced neuronal activation. Notably, the effect of astrocytic Rac1 on memory retrieval was reversible. Our results demonstrate that the normal activity of astrocytic Rac1 is necessary for the activation of neurons and memory formation. Both activation and inactivation of astrocytic Rac1 activity in the BLA reduced the excitability of neurons, and thereby impaired fear memory acquisition and retrieval.

Effects of TRPC1 on epithelial mesenchymal transition in human airway in chronic obstructive pulmonary disease.

BACKGROUND: We investigated the effects of TRPC1 on epithelial mesenchymal transition (EMT) in human airway in chronic obstructive pulmonary disease (COPD). METHODS: A total of 94 patients who underwent lobectomy were selected and divided into COPD (49 cases) and control (45 cases) groups. Immunohistochemistry was applied to detect expression of E-cadherin and vimentin and TRPC1. Correlation of TRPC1 expression with E-cadherin and vimentin expression, and correlations of lung function indicators in COPD patients with expression of TRPC1, E-cadherin, and vimentin were analyzed. Human airway epithelial cells (16HBE) were used for cell experiments; and cigarette smoking extract (CSE) was adopted to establish the COPD model using TRPC1 recombinant plasmids and siRNA. Cells were assigned into the control, CSE, CSE + vector, CSE + TRPC1, CSE + si-NC, and CSE + si-TRPC1 groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were implemented to detect expression of TRPC1, E-cadherin, and vimentin. RESULTS: Compared with the control group, expression of TRPC1 and vimentin significantly increased while expression of E-cadherin decreased in the COPD group, and protein expression of TRPC1 was positively correlated with the protein expression of vimentin but negatively correlated with the protein expression of E-cadherin. Patients exhibiting positive expression of TRPC1 had lower FEV1, FEV1%Pred, and FEV1/FVC, compared with the patients exhibiting negative expression of TRPC1. Compared with the control group, expression of TRPC1 and vimentin increased, whereas expression of E-cadherin decreased in the CSE, CSE + vector, CSE + TRPC1, and CSE + si-NC groups. Compared with the CSE and CSE + vector groups, the expression of TRPC1 and vimentin increased but the expression of E-cadherin decreased in the CSE + TRPC1 group. Compared with the CSE and CSE + si-NC groups, the expression of TRPC1 and vimentin decreased but the expression of E-cadherin increased in the CSE + si-TRPC1 group. No significant differences were observed among the CSE, CSE + vector and CSE + si-NC groups. CONCLUSION: Overexpression of TRPC1 in COPD promoted EMT process and TRPC1 may be a new and interesting focus for COPD new treatment in the future.

Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy.

MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells' sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC.