PARP1 deficiency protects against hyperglycemia-induced neointimal hyperplasia by upregulating TFPI2 activity in diabetic mice.

Diabetes mellitus (DM) promotes neointimal hyperplasia, characterized by dysregulated proliferation and accumulation of vascular smooth muscle cells (VSMCs), leading to occlusive disorders, such as atherosclerosis and stenosis. Poly (ADP-ribose) polymerase 1 (PARP1), reported as a crucial mediator in tumor proliferation and transformation, has a pivotal role in DM. Nonetheless, the function and potential mechanism of PARP1 in diabetic neointimal hyperplasia remain unclear. In this study, we constructed PARP1 conventional knockout (PARP1-/-) mice, and ligation of the left common carotid artery was performed to induce neointimal hyperplasia in Type I diabetes mellitus (T1DM) mouse models. PARP1 expression in the aorta arteries of T1DM mice increased significantly and genetic deletion of PARP1 showed an inhibitory effect on the neointimal hyperplasia. Furthermore, our results revealed that PARP1 enhanced diabetic neointimal hyperplasia via downregulating tissue factor pathway inhibitor (TFPI2), a suppressor of vascular smooth muscle cell proliferation and migration, in which PARP1 acts as a negative transcription factor augmenting TFPI2 promoter DNA methylation. In conclusion, these results suggested that PARP1 accelerates the process of hyperglycemia-induced neointimal hyperplasia via promoting VSMCs proliferation and migration in a TFPI2 dependent manner.

ILF3 is responsible for hyperlipidemia-induced arteriosclerotic calcification by mediating BMP2 and STAT1 transcription.

Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

Study on the mechanism of the Modified Ginseng-Schisandra Decoction (MGSD) in the treatment of recurrent respiratory tract infection (RRTI) based on network pharmacology.

BACKGROUND: The aim of this study was to investigate the mechanism of Modified Ginseng-Schisandra Decoction in the treatment of recurrent respiratory tract infection (RRTI) using network pharmacology. METHODS: To screen the active ingredients of A Modified Ginseng-Schisandra Decoction, TCMSP, TCMID, Batman-TCM and PubChem database were applied. To predict the targets of active ingredients on RRTI, TCMSP, Pubmed, OMIM, Drug Bank, GAD and TTD database were used. The compounds-therapeutic target network was constructed with Cytoscape 3.7.2 software. The STRING database was used to construct a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify potential signal pathways. RESULTS: The 3 main active ingredients of Modified Ginseng-Schisandra Decoction obtained by screening were quercetin, kaempferol, and isoflavone; the main therapeutic targets were PTGS2, ESR1, AR, PPARG, NOS2, and others. Based on the PPI network, we found that the targets of Modified Ginseng-Schisandra Decoction were significantly enriched in (FDR <0.01) cancer pathway, tumor necrosis factor (TNF) signaling pathway, hypoxia-inducible factor (HIF-1) signaling pathway, and others. CONCLUSIONS: Modified Ginseng-Schisandra Decoction can treat RRTI primarily through acting in the signal transduction of some key nodes of cancer pathway and TNF pathway. It exerts a direct or indirect influence on multiple signaling pathways, and has the characteristics of multicomponent, multitarget, and multichannel action.

Clinical observation of the effect of modified Ginseng-Schisandra decoction (MGSD) on trace elements and immune function in children with spleen deficiency syndrome after recurrent respiratory tract infection (RRTI): a randomized controlled trial.

BACKGROUND: Recurrent respiratory tract infection (RRTI) is common disease in childhood, and the incidence rate is increasing in China. The cause is complex, which is related to the physiological characteristics of children's respiratory system and the immature immune function, lack of trace elements and environmental pollution. Immunomodulators and antibiotics are often used to treat RRTI, but the clinical efficacy still needs to be improved. Chinese medicine has unique advantages in the treatment of RRTI. In the clinical treatment of RRTI, the authors often use modified Ginseng-Schisandra decoction (MGSD). In order to study the clinical effect of MGSD on serum trace elements and immune function in children with spleen deficiency syndrome after RRTI, we conducted this clinical observation. METHODS: This is a single-center randomized trial with two parallel groups. Eighty children who developed spleen deficiency syndrome following RRTI were randomly and equally divided into a control group and an observation group. The control group was given Medilac-vita and the observation group was given MGSD. The participants, care givers, and those assessing the outcomes were blinded to group assignment. The treatment course was 4 weeks. Clinical efficacy, traditional Chinese medicine (TCM) syndrome scores, humoral immunity, and trace element index values before and after treatment were compared between the two groups of children. RESULTS: The trial was finished. The total effective rate of the observation group (n=40, 95%) was significantly higher than control group (n=40, 65%) (P<0.05). After treatment, the TCM syndrome scores of the two groups were reduced compared to those before treatment, while the serum immunoglobulin A and G levels were increased (P<0.05); however, the observation group had significantly lower TCM syndrome scores than the control group. Significant improvements in serum immunoglobulins (IgA and IgG) levels, T lymphocyte subsets (CD3+, CD4+, and CD4+/CD8+), and trace elements (Zn and Fe) indicators were observed in the observation group compared to the control group (P<0.05). CONCLUSIONS: The application of MGSD in the treatment of children with spleen deficiency syndrome after RRTI has a definite clinical effect. MGSD can effectively improve the immune function of the patients and the content of the trace elements iron and zinc, and thus has potential value for promotion and application. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047128.

Combined surgical and interventional treatment of tandem carotid artery and middle cerebral artery embolus: A case report.

BACKGROUND: The 2018 American Heart Association/American Stroke Association guidelines for early management of acute ischemic stroke recommend the use of retrievable stents for mechanical thrombectomy in patients with acute internal carotid artery or middle cerebral artery M1 occlusion that can be treated within 6 h from onset. For cases of carotid artery with ipsilateral middle cerebral artery tandem embolization, the operation is more complicated and challenging. We here report a case of a tandem embolism, and the anatomy of the aortic arch was complex. Direct carotid artery incision and thrombectomy can not only prevent the escape of the carotid embolus but also save time during establishment of the thrombectomy access. CASE SUMMARY: The patient was a 70-year-old man. He was admitted to hospital due to sudden inability to speak and inability to move his right limb for 3 h. Imaging confirmed a diagnosis of a tandem embolism in the left carotid artery with left M1 occlusion. Carotid artery incision thrombectomy combined with stent thrombectomy was performed. The operation was successful, and 24 h later the patient was conscious and mentally competent but had motor aphasia. His bilateral limb muscle strength level was 5, and his neurologic severity scores score was 2. CONCLUSION: Carotid artery incision thrombectomy combined with stenting for carotid artery plus cerebral artery tandem embolization is clinically feasible. For patients with a complicated aortic arch and an extremely tortuous carotid artery, carotid artery incision can be chosen to establish the interventional path.

Arterial occlusion to treat basilar artery dissecting aneurysm.

OBJECT: To explore the clinical feasibility of employing occlusion to treat basilar artery dissecting aneurysm. METHODS: One patient, male and 46 years old, suffered transient numbness and weakness on the right limbs. Cerebral angiography indicated basilar artery dissecting aneurysm. The patient underwent the stent-assisted coil embolization of aneurysm and the result is satisfactory. Digital subtraction angiography (DSA) reviews were performed at 1 month and 4.5 months, respectively after the operation and indicate that the basilar artery is unobstructed and there was no recurrence of the aneurysm. DSA review 1 year after the first treatment indicates the aneurysm recurrence, stent-assisted coils dense embolization of aneurysm was performed again and the result was satisfactory. Ten months after the second operation, DSA review found the basilar artery aneurysm recurrence again and occlusion of the basilar artery was performed. RESULTS: The basilar artery occlusion was effective. The bilateral posterior inferior cerebellar arteries and the bilateral posterior cerebral arteries are unobstructed. Five months of follow-up found that the patient recovered well. DSA reviews performed 5 months after occlusion indicate no recurrence of the aneurysm. CONCLUSIONS: Occlusion to treat basilar artery dissecting aneurysm is clinically feasible, but surgical indications should be considered strictly.

MicroRNA-184 promotes proliferation ability of glioma cells by regulating FOXO3.

OBJECTIVES: To investigate the effect of microRNA (miR-184) on regulating the genesis, development and proliferation of glioma cells. METHODS: Lipidosome was used to transfect miR-184 mimic and inhibitor to glioma cell line, and the cell proliferation ability changes were determined by MTT and plate cloning experiment after the transfection. WB test was used to measure the levels of cyclinD1, p27 and FOXO3. Meanwhile, QPCR was used to detect miR-184 expression in glioma cell line, glioma tissues and adjacent tissues. Luciferase experiment was used to test 3'UTR gene targeting regulation of miR-184 and FOXO3. RESULTS: QPCR results showed a significant lower miR-184 expression level in glioma cell line and glioma tissues than that in juxtacancerous tissue. MTT and plate cloning experiments have shown that after over-expressing of miR-184, the cell proliferation capacity of glioma U87 and T98G was significantly increased, which was significantly inhibited after the inhibition of miR-184. WB results showed a lower expression level of p27 in U87 and T98G cells, and a higher expression level of cyclinD1 after over-expressing of miR-184 was observed. However, a lower expression level of cyclinD1 and a higher expression level of p27 after the inhibition of miR-184. The luciferase activity was inhibited after the over-expressing of miR-184. CONCLUSIONS: MiR-184 can affect the proliferation abilities of glioma cells and regulate the cell cycle related protein. It plays an important role in the occurrence and development of gliomas.

Association of ERCC1 rs3212986 & ERCC2 rs13181 polymorphisms with the risk of glioma.

OBJECTIVE: : Several previous studies have reported the role variant of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms in the risk of glioma, but the results of these studies are inconsistent. Therefore, we aimed to conduct a meta-analysis to investigate the role of ERCC1 rs3212986 and ERCC2 rs13181 on the risk of glioma. METHODS: A comprehensive research was conducted through the databases of Pubmed, EMBASE and the China National Knowledge Infrastructure (CNKI) platforms until June 1, 2014, including 14 eligible case-control studies. RESULTS: Our meta-analysis found that ERCC1 rs3212986 AA genotype was significantly associated with increased risk of glioma compared with CC genotype, and the pooled OR (95%CI) was 1.29(1.07-1.55). By subgroup analysis, ERCC1 rs3212986 AA genotype was found to be significantly correlated with increased glioma risk in Chinese population (OR=1.37, 95%CI=1.07, 1.55), Similarly, we found that ERCC2 rs13181 GT and TT genotypes were significantly associated with increased risk of glioma in Chinese population, with ORs(95%CI) of 1.47(1.17-1.85) and 1.50(1.02-2.22). But ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms had no significant association with glioma risk in Caucasian populations. By begg's funnel plot, we found that no publication bias was existed in this meta-analysis. CONCLUSION: Our meta-analysis suggested that ERCC1 rs3212986 and ERCC2 rs13181 polymorphism play an important risk factor for brain tumor development in Chinese population, but no association in Caucasian populations.

Endoscopic and microscopic anatomy of the superior sagittal sinus and torcular herophili.

Surgery of the superior sagittal sinus (SSS) is a challenging areas for neurosurgeons. To better understand the anatomy of the SSS, we examined the chordae and arachnoid granulations in the lumen of the SSS and torcular herophili with the aid of an endoscope and a microscope, and re-evaluated the role of the chordae Willisii in preventing blood backflow. We prepared 10 SSS from fresh human cadavers during autopsies. After the cranial vaults were removed, an endoscope was inserted into the lumen of the sinus to examine the structures and morphological features of the chordae Willisii, and the topographic distribution of the arachnoid granulations. The sinuses were subsequently opened using standard anatomical methods and the intraluminal structures of the dural sinus were subjected to microanatomic analysis. In another five formalin-embalmed cadaver heads, blue latex was injected from the posterior end of the SSSs to observe filling of the SSS tributaries. We identified three types of chordae in the lumen of the SSS: valve-like chordae (48.3% of all chordae), followed by trabecular (31.5%) and laminar (20.2%) chordae. The laminar chordae at the posterior end of the SSS divide the sinus into two separate channels of different sizes. Similar structures were also seen in the lumen of the torcular herophili. The majority of arachnoid granulations were found as digitations in the lumen at the lateral wall or lateral recess of the middle segment of the SSS. Microscopic examination of the intraluminal structures of the SSS confirmed endoscopic findings. In the injection test we found that the SSS tributaries could be filled retrogradely with artificial dye, suggesting that the function of valve-like chordae in preventing the backflow of blood is restricted only to physiological conditions. Thus, we could visualize and examine endoscopically the intact intraluminal structures of the SSS, which may have therapeutic or diagnostic significance.