TM6SF2 reduces lipid accumulation in vascular smooth muscle cells by inhibiting LOX-1 and CD36 expression.

TM6SF2, predominantly expressed in the liver and intestine, is closely associated with lipid metabolism. We have demonstrated the presence of TM6SF2 in VSMCs within human atherosclerotic plaques. Subsequent functional studies were conducted to investigate its role in lipid uptake and accumulation in human vascular smooth muscle cells (HAVSMCs) using siRNA knockdown and overexpression techniques. Our results showed that TM6SF2 reduced lipid accumulation in oxLDL-stimulated VSMCs, likely through the regulation of lectin-like oxLDL receptor 1 (LOX-1) and scavenger receptor cluster of differentiation 36 (CD36) expression. We concluded that TM6SF2 plays a role in HAVSMC lipid metabolism with opposing effects on cellular lipid droplet content by downregulation of LOX-1 and CD36 expression.

[Collection methods, stylistic layout and value of extraordinary points in Doutaishi Zhenjing (Master Dou's Canon of Acupuncture)].

The literature source, collection methods and stylistic layout, value and influence of 32 extraordinary points in Doutaishi Zhenjing (Master Dou's Canon of Acupuncture) were collected. The sources of the literature are extensive. The collection methods include 5 aspects, named inheritance, integration and repair; name rectification, identification and differentiation; new point explication on the base of extraordinary points; well arrangement of points and mutual use of three methods for stylistic layout; as well as integrative illustration with text and picture, and determined location. In reference to the holistic layout of name, location, techniques of acupuncture and moxibustion and indications of extraordinary points in Doutaishi Zhenjing (Master Dou's Canon of Acupuncture), it is the first time to make a standardized and unified collection of extraordinary points, which is valuable in the historical literature, the theoretic research and clinical practice of extraordinary points. It brings a great impact on the special articles or books after the Yuan dynasty and even the establishment of national standards at present.

[Relationship between DOU Han-qing of the Jin and Yuan Dynasty and Taoist].

In order to explore the culture factors of the construction of acupuncture theory of DOU Han-qing, the medical master of the Jin and Yuan Dynasty, the authors studied the relationship between DOU Han-qing and Taoist by collecting DOU 's life material. With manual retrieval, some ancient historical literature was obtained. Additionally, Yijing Huiyuan: Zhenjiu Yuanshu: Dou Taishi Michuan Mihua Zhenjing Qiongyao Baojian, written by WU Jia-yan in the Ming Dynasty, collected in Japan, was analyzed. It was found that DOU Han-qing's acupuncture and moxibustion was influenced by Suwen Wangpian: Cifalun, the Taoism medicine of the early stage of the Song Dynasty, as well as by Jiaojing Baxue, passed on by SONG Zi-hua, the hermit. DOU Han-qing had been in contact with FAN Zhi-ying of the Taoist, but there was no clear record relevant with medicine. Dou Taishi Michuan Mihua Zhenjing Qiongyao Baojian may be the compilation by Taoism medical master, on the base DOU 's acupuncture and moxibustion. There is a kind of mutual influence and mutual promotion relationship between DOU Han-qing and Taoist.

Potential protective effects of red yeast rice in endothelial function against atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice (RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.

PCSK9: A novel inflammation modulator in atherosclerosis?

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low-density lipoprotein receptor (LDLR) for endocytosis and lysosome degradation in the liver, resulting in an increasing in circulating LDL-cholesterol (LDL-c) level. Since a PCSK9 induced increase in plasma LDL-c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL-c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.

TM6SF2: A novel target for plasma lipid regulation.

Transmembrane 6 superfamily 2 (TM6SF2), a gene identified at the locus 19p12, has been recognized to regulate plasma lipids. Here, we provide an overview of the roles of TM6SF2 as a novel target for plasma lipid regulation. We first review the association of TM6SF2 variant with plasma lipid traits, cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Then, we present an overview about the in vivo validation of TM6SF2 as a regulator of plasma lipid levels using mice, with overexpression or knockdown/knockout of TM6SF2. Thereafter, we discuss the mechanisms underlying TM6SF2 regulation of lipid metabolism involving intestinal cholesterol absorption and hepatic cholesterol biosynthesis and transport. In conclusion, increasing evidence suggests that TM6SF2 may be a major regulator of plasma lipid levels and become a therapeutic target in cardiovascular disease.

New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression. METHODS: We examined whether PCSK9 silencing via transduction with the lentivirus-mediated PCSK9 shRNA (LV-PCSK9 shRNA) vector affects the formation of vascular lesions in hyperlipidemia-induced atherosclerosis in apolipoprotein E knockout (apoE KO) mice. In vitro, the effects of PCSK9 on oxLDL-induced macrophages inflammation were investigate using LV-PCSK9 and LV-PCSK9 shRNA for PCSK9 overexpression and PCSK9 silencing. RESULTS: Immunohistochemical analysis showed that PCSK9 expression increased within atherosclerotic plaques in apoE KO mice. These in vivo results showed that the LV-PCSK9 shRNA group of mice developed less aortic atherosclerotic plaques compared with the control group. These lesions also had the reduced number of macrophages and decreased expression of vascular inflammation regulators, such as tumor necrosis factor-α, interleukin 1 beta, monocyte chemoattractant protein-1, toll-like receptor 4 and nuclear factor kappa B (NF-κB). We further showed that PCSK9 overexpression in macrophages in vitro increased the secretion of oxLDL-induced proinflammatory cytokines. PCSK9 overexpression upregulated TLR4 expression and increased p-IκBα levels, IkBα degradation, and NF-κB nuclear translocation in macrophages, but PCSK9 knockdown had the opposite effects in oxLDL-treated macrophages. CONCLUSIONS: PCSK9 gene interference could suppress atherosclerosis directly through decreasing vascular inflammation and inhibiting the TLR4/NF-κB signaling pathway without affecting plasma cholesterol level in high-fat diet-fed apoE KO mice. PCSK9 may be an inflammatory mediator in the pathogenesis of atherosclerosis.

[Study on the origin of Dou Han-qing's academic thought of acupuncture and moxibustion].

The origin of Dou Han-qing's academic thought of acupuncture and moxibustion is studied by analysis on relative contents in the books Weisheng Baojian, Jisheng Bacui and Zhenjiu Sishu Zhenjing Zhinan and the two papers "On reinforcing-reducing manipulation" and "Questions and answers of qi and blood", holding that DOU Han-qing's academic thought of acupuncture and moxibustion is influenced more by Suwen (Plain Questions) and Nanjing (Classic on Medical Problems), not by Lingshu (Miraculous Pivot).

[Textual research and differentiation of Dou Han-qing's works catalogue].

This paper aims at probing into evolving course of DOU Han-qing's works catalogue. On the basis of summarizing and referring to study achievements of our predecessors, through analysis of book lists and relative works and chapters, it is hold that the catalogue which were not attained by ZHULiang-neng possibly are the contents of acupuncture reinforcing and reducing methods; the books printed and published by ZHULiang-neng include the contents of both channels and acupoints; the book, Zhinan, which was attained by DOUGui-fang, includes the content catalogue of needling methods; Fu Zhenjiu Zashuo in Zhenjiu Sisu. Zhenjiu Zhinan also were extracted by DOU Gui-fang from Illustrated Manual of Acupoints of the Bronze Figure, and The Zhenjiu Biji Taiyi Zhi Tuxu and Dongzhi Yezhe Gongshuo should belong to The Fu Zhenjiu Zashuo.