Guidelines on the diagnosis and treatment of diabetic foot Yongquan Gu Vascular Investigation and Therapy 2019 2(3):55-62 Diabetic foot is one of the serious chronic complications caused by diabetes mellitus. The guidelines introduce the fundamental concepts of diabetic foot, distinction between diabetic lower-extremity ischemia and lower-extremity arteriosclerosis with concurrent diabetes mellitus, pathological features of diabetic foot lesions, and the prognosis. This article focuses on the diagnosis and treatment of diabetic foot, including endovascular arterial revascularization of lower extremity, arterial bypass reconstruction, and stem cell transplantation. The selection of therapeutic schemes for the larger, middle, and small artery lesions and the perioperative management are also discussed in detail.

Thymopentin promotes ovarian angiogenesis in mice by activating N6-methyladenosine (m6A) RNA modification of key factors in the Notch/Tie1 pathway Junjun Tao, Jiajia Lin, Xiaoli Nie, William Huang, Jianming Guo, Te Liu Vascular Investigation and Therapy 2019 2(3):63-72 Abstract: BACKGROUND: Premature ovarian failure (POF) is a typical condition of pathological ovarian ageing. Injuries and atrophies of blood vessels in the ovaries can lead to ovarian insufficiency, but the underlying mechanism remains unclear. AIMS: This study investigated the epigenetic mechanism by which thymopentin (TP-5) activated ovarian angiogenesis to achieve its effects on POF. MATERIALS AND METHODS: The qPCR, western blot and immunofluorescence staining were used to detecte the expression levels of gene. The hematoxylin and eosin stainingwas used to histopathological examination. The RNA-Seq sequencing was used to transcriptome detection. RESULTS: First, pathological examination revealed that TP-5 significantly increased ovary weight in the cyclophosphamide-induced POF mouse model. The proportion of atretic follicles was reduced, and the level of E2 in the peripheral blood was elevated. Meanwhile, immunofluorescence staining showed that TP-5 increased protein expression of CD31 and Tie1 in the ovarian tissues of mice with POF, suggesting that TP-5 could induce ovarian angiogenesis. RNA-Seq sequencing results suggested that TP-5 could induce the high level of Notch/Tie2 pathway expression that is associated with angiogenesis in ovarian tissues. qPCR and western blotting showed significantly increased expression of METTL3, a methyltransferase that catalyses the formation of N6-methyladenosine (m6A) in RNA. Meanwhile, the results of the dot blot suggested that the overall RNA methylation level was significantly higher in the ovarian tissues of mice in the TP-5 group than in the control group. Finally, RIP-PCR analysis showed that specific sites in the 3'-untranslated region (3'UTR) of the mRNA of key factors in the Notch/Tie2 pathway were hypermethylated in the ovaries of mice in the TP-5 treatment group. CONCLUSION: Therefore, this study demonstrated that TP-5 exerted its therapeutic effect on POF by stimulating angiogenesis. The mechanism of action is the promotion of the expression of RNA m6A methyltransferases by TP5, which increases the overall RNA m6A methylation level in mouse ovarian tissue. Specifically, the methylation ofspecific m6A sites in the 3'UTR of the RNA of key factors in the Notch/Tie2 pathway increased, which enhanced their stability and expression levels, leading to the induction of angiogenesis.

Multiple functions of cold-inducible RNA-binding protein in biological systems Gang Li, Peixian Gao, Kun Luo, Hua Zhou, Yuxiang He, Hai Yuan, Xuejun Wu Vascular Investigation and Therapy 2019 2(3):73-77 Cold-inducible RNA-binding protein (CIRP) is an 18-kDa nuclear protein belonging to the family of cold-shock proteins. It is widely expressed in various tissues and upregulated in response to various cellular stresses. Originally, CIRP was found to stabilize specific mRNAs to facilitate their translation, which results in a survival advantage for cells under stress. Hypothermia-induced CIRP has been shown to protect the neuronal system. Recently, CIRP was found to be a multifunctional protein. In addition to acting as a damage-associated molecular pattern molecule to promote inflammation, it was also found to affect tumorigenesis. CIRP was also found to regulate telomerase activity and cardiac repolarization. Therefore, biological activities of CIRP in novel systems should receive more attention. This review will provide a brief introduction to the recent studies of CIRP with the aim of inspiring future research of novel CIRP functions.

Antidotes for the new oral anticoagulant drugs! Jawed Fareed, Fakiha Siddiqui, Eduardo Ramacciotti, Alfonso Tafur Vascular Investigation and Therapy 2019 2(3):78-81 The introduction of direct oral anticoagulant drugs has added a new dimension to the management of thrombotic and cardiovascular diseases. Although clinical useful, the use of these drugs has been associated with bleeding complications of varying magnitude. Until recently, there was no antidote available for the control of bleeding associated with DOAC's. Such traditional approaches as the use of blood products and mechanical methods have been used to control bleeding in past. Molecular approaches have resulted in the development of specific antidotes for the oral anti-Xa and anti-IIa drugs. Andexanet alfa is a molecularly modified recombinant human factor Xa which is developed as an antidote for rivaroxaban and apixaban. Praxbind is an antibody which neutralizes dabigatran. Both agents have approved by the FDA and the European Medicine Agency, while these two agents are valuable in the management of bleeding with DOAC's, their use is associated with various adverse responses. Since both agents are proteins, antibody generation and interactions with endogenous proteins may also contribute to some of the observed adverse effects. The clinical data on their use is rather limited and additional studies are warranted to optimize their use. A global antidote, Ciraparantag, (PER977) is also developed for the neutralization of DOAC's. Both the activated and non-activated forms of prothrombin complexes are reportedly effective as an antidote for DOAC's. Additional studies are needed to develop guidelines for the safe use of antidotes to minimize the observed complications with the use of antidotes.

Multiple intraventricular brain metastasis in a case of non-small cell lung carcinoma Rashmeet Kaur, Simmi Aggarwal, Sonali Gadhavi, Anshul Dahuja, Paramdeep Singh Vascular Investigation and Therapy 2019 2(3):82-84 Intraventricular metastasis is a rare entity encountered in very few malignancies. Although the renal cell carcinoma is the most common primary causing this rare event, due to overall more incidences of lung carcinomas, the intraventricular metastasis by lung cancer is the most common cause. Our patient was a diagnosed case of non-small cell carcinoma and non-small cell lung cancer. (NSCLC) with an advanced stage of disease at the time of presentation that resulted in a poor prognosis. The most common metastatic site in non-small cell carcinoma is bone, followed by the lungs, brain, liver, and adrenal glands. The treatment for metastatic NSCLC consists of systemic therapy using cytotoxic and molecularly-targeted agents and palliative radiotherapy for symptomatic metastases. Surgical resection or gamma knife can be considered for those with isolated brain metastasis for better prognosis.