ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment.

BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.

ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.

BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.

NDP52 SUMOylation contributes to low-dose X-rays-induced cardiac hypertrophy through PINK1/Parkin-mediated mitophagy via MUL1/SUMO2 signalling.

Radiation-induced heart damage caused by low-dose X-rays has a significant impact on tumour patients' prognosis, with cardiac hypertrophy being the most severe noncarcinogenic adverse effect. Our previous study demonstrated that mitophagy activation promoted cardiac hypertrophy, but the underlying mechanisms remained unclear. In the present study, PARL-IN-1 enhanced excessive hypertrophy of cardiomyocytes and exacerbated mitochondrial damage. Isobaric tags for relative and absolute quantification-based quantitative proteomics identified NDP52 as a crucial target mediating cardiac hypertrophy induced by low-dose X-rays. SUMOylation proteomics revealed that the SUMO E3 ligase MUL1 facilitated NDP52 SUMOylation through SUMO2. Co-IP coupled with LC-MS/MS identified a critical lysine residue at position 262 of NDP52 as the key site for SUMO2-mediated SUMOylation of NDP52. The point mutation plasmid NDP52K262R inhibited mitophagy under MUL1 overexpression, as evidenced by inhibition of LC3 interaction with NDP52, PINK1 and LAMP2A. A mitochondrial dissociation study revealed that NDP52K262R inhibited PINK1 targeting to endosomes early endosomal marker (EEA1), late/lysosome endosomal marker (LAMP2A) and recycling endosomal marker (RAB11), and laser confocal microscopy confirmed that NDP52K262R impaired the recruitment of mitochondria to the autophagic pathway through EEA1/RAB11 and ATG3, ATG5, ATG16L1 and STX17, but did not affect mitochondrial delivery to lysosomes via LAMP2A for degradation. In conclusion, our findings suggest that MUL1-mediated SUMOylation of NDP52 plays a crucial role in regulating mitophagy in the context of low-dose X-ray-induced cardiac hypertrophy. Two hundred sixty-second lysine of NDP52 is identified as a key SUMOylation site for low-dose X-ray promoting mitophagy activation and cardiac hypertrophy. Collectively, this study provides novel implications for the development of therapeutic strategies aimed at preventing the progression of cardiac hypertrophy induced by low-dose X-rays.

Risk factors for high CAD-RADS scoring in CAD patients revealed by machine learning methods: a retrospective study.

Objective: This study aimed to investigate a variety of machine learning (ML) methods to predict the association between cardiovascular risk factors and coronary artery disease-reporting and data system (CAD-RADS) scores. Methods: This is a retrospective cohort study. Demographical, cardiovascular risk factors and coronary CT angiography (CCTA) characteristics of the patients were obtained. Coronary artery disease (CAD) was evaluated using CAD-RADS score. The stenosis severity component of the CAD-RADS was stratified into two groups: CAD-RADS score 0-2 group and CAD-RADS score 3-5 group. CAD-RADS scores were predicted with random forest (RF), k-nearest neighbors (KNN), support vector machines (SVM), neural network (NN), decision tree classification (DTC) and linear discriminant analysis (LDA). Prediction sensitivity, specificity, accuracy and area under the curve (AUC) were calculated. Feature importance analysis was utilized to find the most important predictors. Results: A total of 442 CAD patients with CCTA examinations were included in this study. 234 (52.9%) subjects were CAD-RADS score 0-2 group and 208 (47.1%) were CAD-RADS score 3-5 group. CAD-RADS score 3-5 group had a high prevalence of hypertension (66.8%), hyperlipidemia (50%) and diabetes mellitus (DM) (35.1%). Age, systolic blood pressure (SBP), mean arterial pressure, pulse pressure, pulse pressure index, plasma fibrinogen, uric acid and blood urea nitrogen were significantly higher (p < 0.001), and high-density lipoprotein (HDL-C) lower (p < 0.001) in CAD-RADS score 3-5 group compared to the CAD-RADS score 0-2 group. Nineteen features were chosen to train the models. RF (AUC = 0.832) and LDA (AUC = 0.81) outperformed SVM (AUC = 0.772), NN (AUC = 0.773), DTC (AUC = 0.682), KNN (AUC = 0.707). Feature importance analysis indicated that plasma fibrinogen, age and DM contributed most to CAD-RADS scores. Conclusion: ML algorithms are capable of predicting the correlation between cardiovascular risk factors and CAD-RADS scores with high accuracy.

SUMOylation targeting mitophagy in cardiovascular diseases.

Small ubiquitin-like modifier (SUMO) plays a key regulatory role in cardiovascular diseases, such as cardiac hypertrophy, hypertension, atherosclerosis, and cardiac ischemia-reperfusion injury. As a multifunctional posttranslational modification molecule in eukaryotic cells, SUMOylation is essentially associated with the regulation of mitochondrial dynamics, especially mitophagy, which is involved in the progression and development of cardiovascular diseases. SUMOylation targeting mitochondrial-associated proteins is admittedly considered to regulate mitophagy activation and mitochondrial functions and dynamics, including mitochondrial fusion and fission. SUMOylation triggers mitochondrial fusion to promote mitochondrial dysfunction by modifying Fis1, OPA1, MFN1/2, and DRP1. The interaction between SUMO and DRP1 induces SUMOylation and inhibits lysosomal degradation of DRP1, which is further involved in the regulation of mitochondrial fission. Both SUMOylation and deSUMOylation contribute to the initiation and activation of mitophagy by regulating the conjugation of MFN1/2 SERCA2a, HIF1α, and PINK1. SUMOylation mediated by the SUMO molecule has attracted much attention due to its dual roles in the development of cardiovascular diseases. In this review, we systemically summarize the current understanding underlying the expression, regulation, and structure of SUMO molecules; explore the biochemical functions of SUMOylation in the initiation and activation of mitophagy; discuss the biological roles and mechanisms of SUMOylation in cardiovascular diseases; and further provide a wider explanation of SUMOylation and deSUMOylation research to provide a possible therapeutic strategy for cardiovascular diseases. Considering the precise functions and exact mechanisms of SUMOylation in mitochondrial dysfunction and mitophagy will provide evidence for future experimental research and may serve as an effective approach in the development of novel therapeutic strategies for cardiovascular diseases. Regulation and effect of SUMOylation in cardiovascular diseases via mitophagy. SUMOylation is involved in multiple cardiovascular diseases, including cardiac hypertrophy, hypertension, atherosclerosis, and cardiac ischemia-reperfusion injury. Since it is expressed in multiple cells associated with cardiovascular disease, SUMOylation can be regulated by numerous ligases, including the SENP family proteins PIAS1, PIASy/4, UBC9, and MAPL. SUMOylation regulates the activation and degradation of PINK1, SERCA2a, PPARγ, ERK5, and DRP1 to mediate mitochondrial dynamics, especially mitophagy activation. Mitophagy activation regulated by SUMOylation further promotes or inhibits ventricular diastolic dysfunction, perfusion injury, ventricular remodelling and ventricular noncompaction, which contribute to the development of cardiovascular diseases.

The role of metal ions in the Golgi apparatus.

The Golgi apparatus is a membrane-bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure and function have attracted ever-increasing attention from researchers. Recently, it has been demonstrated that metal ions are necessary for the Golgi apparatus to maintain its proper structure and functions. Given that metal ions play an important role in various biological processes, their abnormal homeostasis is related to many diseases. Therefore, in this paper, we reviewed the uptake and release mechanisms of the Golgi apparatus Ca2+ , Cu, and Zn2+ . Furthermore, we describe the diseases associated with Golgi apparatus Ca2+ , Cu, and Zn2+ imbalance.

SUMO2-mediated SUMOylation of SH3GLB1 promotes ionizing radiation-induced hypertrophic cardiomyopathy through mitophagy activation.

Hypertrophic cardiomyopathy (HC) is characterized by the enlargement of individual cardiomyocytes, which is a typical pathophysiological process that occurs in various cardiovascular diseases. Ionizing radiation (IR) is an important independent risk factor for hypertrophic cardiomyopathy, but the underlying molecular mechanism is still unclear. In the present study, we aimed to clarify the role of IR in promoting cardiac hypertrophy and investigate the mechanism by which the SUMO2-mediated SUMOylation of SH3GLB1 affects mitophagy in IR-induced cardiac hypertrophy. In vivo, IR promoted cardiac hypertrophy by activating mitophagy. In vitro, IR upregulated PINK1 and Parkin protein expression and damaged mitochondrial morphological structure. We further demonstrated that SH3GLB1 deficiency inhibited mitophagy activation and restored mitochondrial cristae, revealing a regulatory role of SH3GLB1 in cardiac hypertrophy. IR promoted interactions between SH3GLB1 and mitochondrial membrane proteins, such as MFN1/2, TOM20 and Drp1, further indicating that the mechanism by which SH3GLB1 functions in cardiac hypertrophy might involve mitophagy. A bioinformatics prediction found that SUMO2 could SUMOylate SH3GLB1 at position K82. Consistent with this finding, both co-IP assays and laser confocal microscopy showed that IR promoted the interaction and colocalization of SUMO2 and SH3GLB1. In summary, our study identifies IR as an important factor that promotes hypertrophic cardiomyopathy by accelerating the activation of mitophagy through the SUMO2-mediated SUMOylation of SH3GLB1; thus, IR exerts dual therapeutic effects in the treatment of thoracic tumours with long-term radiotherapy. Additionally, this study provides novel treatment strategies and targets for preventing the hypertrophic cardiomyopathy caused by thoracic tumour radiotherapy. Furthermore, SH3GLB1 may be a promising experimental target for the development of strategies for treating cardiovascular diseases caused by IR.

Golgi stress response: A regulatory mechanism of Golgi function.

The organelle of eukaryotes is a finely regulated system. Once disturbed, it activates the specific autoregulatory systems, namely, organelle autoregulation. Among which, the Golgi stress response accounts for one. When the abundance and capacity of the Golgi apparatus are insufficient compared with cellular demand, the Golgi stress response is activated to enhance the function of the Golgi apparatus. Although the molecular mechanism of the Golgi stress response has not been well characterized yet, it seems to be an important part of the mammalian stress response. In this review, we discuss the current status of research on the six pathways of the mammalian Golgi stress response (the TFE3, heat shock protein 47, CREB3, E26 transformation specific, proteoglycan, and mucin pathways), which regulate the general function of the Golgi apparatus, anti-apoptosis, pro-apoptosis, proteoglycan glycosylation, and mucin glycosylation, respectively.

Sestrin2 as a potential therapeutic target for cardiovascular diseases.

Sestrin2 is a cysteine sulfinyl reductase that plays crucial roles in regulation of antioxidant actions. Sestrin2 provides cytoprotection against multiple stress conditions, including hypoxia, endoplasmic reticulum (ER) stress and oxidative stress. Recent research reveals that upregulation of Sestrin2 is induced by various transcription factors such as p53 and activator protein 1 (AP-1), which further promotes AMP-activated protein kinase (AMPK) activation and inhibits mammalian target of rapamycin protein kinase (mTOR) signaling. Sestrin2 triggers autophagy activity to reduce cellular reactive oxygen species (ROS) levels by promoting nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) activation and Kelch-like ECH-associated protein 1 (Keap1) degradation, which plays a pivotal role in homeostasis of metabolic regulation. Under hypoxia and ER stress conditions, elevated Sestrin2 expression maintains cellular homeostasis through regulation of antioxidant genes. Sestrin2 is responsible for diminishing cellular ROS accumulation through autophagy via AMPK activation, which displays cardioprotection effect in cardiovascular diseases. In this review, we summarize the recent understanding of molecular structure, biological roles and biochemical functions of Sestrin2, and discuss the roles and mechanisms of Sestrin2 in autophagy, hypoxia and ER stress. Understanding the precise functions and exact mechanism of Sestrin2 in cellular homeostasis will provide the evidence for future experimental research and aid in the development of novel therapeutic strategies for cardiovascular diseases.

Bnip3 in mitophagy: Novel insights and potential therapeutic target for diseases of secondary mitochondrial dysfunction.

The present review is a summary of the recent literature concerning Bnip3 expression, function, and regulation, along with its implications in mitochondrial dysfunction, disorders of mitophagy homeostasis, and development of diseases of secondary mitochondrial dysfunction. As a member of the Bcl-2 family of cell death-regulating factors, Bnip3 mediates mPTP opening, mitochondrial potential, oxidative stress, calcium overload, mitochondrial respiratory collapse, and ATP shortage of mitochondria from multiple cells. Recent studies have discovered that Bnip3 regulates mitochondrial dysfunction, mitochondrial fragmentation, mitophagy, cell apoptosis, and the development of lipid disorder diseases via numerous cellular signaling pathways. In addition, Bnip3 promotes the development of cardiac hypertrophy by mediating inflammatory response or the related signaling pathways of cardiomyocytes and is also responsible for raising abnormal mitophagy and apoptosis progression through multiple molecular signaling pathways, inducing the pathogenesis and progress of hepatocellular carcinoma (HCC). Different molecules regulate Bnip3 expression at both the transcriptional and post-transcriptional level, leading to mitochondrial dysfunction and unbalance of mitophagy in hepatocytes, which promotes the development of non-alcoholic fatty liver disease (NAFLD). Thus, Bnip3 plays an important role in mitochondrial dysfunction and mitophagy homeostasis and has emerged as a promising therapeutic target for diseases of secondary mitochondrial dysfunction.

Endoplasmic reticulum stress and focused drug discovery in cardiovascular disease.

Endoplasmic reticulum (ER) is an intracellular membranous organelle involved in the synthesis, folding, maturation and post-translation modification of secretory and transmembrane proteins. Therefore, ER is closely related to the maintenance of intracellular homeostasis and the good balance between health and diseases. Endoplasmic reticulum stress (ERS) occurs when unfolded/misfolded proteins accumulate after disturbance of ER environment. In response to ERS, cells trigger an adaptive response called the Unfolded protein response (UPR), which helps cells cope with the stress. In recent years, a large number of studies show that ERS can aggravate cardiovascular diseases. ERS-related proteins expression in cardiovascular diseases is on the rise. Therefore, down-regulation of ERS is critical for alleviating symptoms of cardiovascular diseases, which may be used in the near future to treat cardiovascular diseases. This article reviews the relationship between ERS and cardiovascular diseases and drugs that inhibit ERS. Furthermore, we detail the role of ERS inhibitors in the treatment of cardiovascular disease. Drugs that inhibit ERS are considered as promising strategies for the treatment of cardiovascular diseases.

Long-term adenosine A1 receptor activation-induced sortilin expression promotes α-synuclein upregulation in dopaminergic neurons.

Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases. However, the pathogenesis underlying long-term adenosine A1 receptor activation-induced neurodegeneration remains unclear. In this study, rats were intraperitoneally injected with 5 mg/kg of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) for five weeks. The mobility of rats was evaluated by forced swimming test, while their cognitive capabilities were evaluated by Y-maze test. Expression of sortilin, α-synuclein, p-JUN, and c-JUN proteins in the substantia nigra were detected by western blot analysis. In addition, immunofluorescence staining of sortilin and α-synuclein was performed to detect expression in the substantia nigra. The results showed that, compared with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (5 mg/kg) + CPA co-treated rats, motor and memory abilities were reduced, surface expression of sortin and α-synuclein in dopaminergic neurons was reduced, and total sortilin and total α-synuclein were increased in CPA-treated rats. MN9D cells were incubated with 500 nM CPA alone or in combination with 10 µM SP600125 (JNK inhibitor) for 48 hours. Quantitative real-time polymerase chain reaction analysis of sortilin and α-synuclein mRNA levels in MN9D cells revealed upregulated sortilin expression in MN9D cells cultured with CPA alone, but the combination of CPA and SP600125 could inhibit this expression. Predictions made using Jasper, PROMO, and Alibaba online databases identified a highly conserved sequence in the sortilin promoter that was predicted to bind JUN in both humans and rodents. A luciferase reporter assay of sortilin promoter plasmid-transfected HEK293T cells confirmed this prediction. After sortilin expression was inhibited by sh-SORT1, expression of p-JUN and c-JUN was detected by western blot analysis. Long-term adenosine A1 receptor activation levels upregulated α-synuclein expression at the post-transcriptional level by affecting sortilin expression. The online tool Raptor-X-Binding and Discovery Studio 4.5 prediction software predicted that sortilin can bind to α-synuclein. Co-immunoprecipitation revealed an interaction between sortilin and α-synuclein in MN9D cells. Our findings indicate that suppression of prolonged adenosine A1 receptor activation potently inhibited sortilin expression and α-synuclein accumulation, and dramatically improved host cognition and kineticism. This study was approved by the University Committee of Animal Care and Supply at the University of Saskatchewan (approval No. AUP#20070090) in March 2007 and the Animals Ethics Committee of University of South China (approval No. LL0387-USC) in June 2017.

A microRNA­24­to­secretagogin regulatory pathway mediates cholesterol­induced inhibition of insulin secretion.

Hypercholesterolemia is a key factor leading to ß­cell dysfunction, but its underlying mechanisms remain unclear. Secretagogin (Scgn), a Ca2+ sensor protein that is expressed at high levels in the islets, has been shown to play a key role in regulating insulin secretion through effects on the soluble N­ethylmaleimide­sensitive factor attachment receptor protein complexes. However, further studies are required to determine whether Scgn plays a role in hypercholesterolemia­associated ß­cell dysfunction. The present study investigated the involvement of a microRNA­24 (miR­24)­to­Scgn regulatory pathway in cholesterol­induced ß­cell dysfunction. In the present study, MIN6 cells were treated with increasing concentrations of cholesterol and then, the cellular functions and changes in the miR­24­to­Scgn signal pathway were observed. Excessive uptake of cholesterol in MIN6 cells increased the expression of miR­24, resulting in a reduction in Sp1 expression by directly targeting its 3' untranslated region. As a transcriptional activator of Scgn, downregulation of Sp1 decreased Scgn levels and subsequently decreased the phosphorylation of focal adhesion kinase and paxillin, which is regulated by Scgn. Therefore, the focal adhesions in insulin granules were impaired and insulin exocytosis was reduced. The present study concluded that a miR­24­to­Scgn pathway participates in the mechanism regulating cholesterol accumulation­induced ß­cell dysfunction.

Sortilin promotes macrophage cholesterol accumulation and aortic atherosclerosis through lysosomal degradation of ATP-binding cassette transporter A1 protein.

Sortilin is closely associated with hyperlipidemia and the risk of atherosclerosis (AS). The role of sortilin and the underlying mechanism in peripheral macrophage are not fully understood. In this study, we investigated the effect of macrophage sortilin on ATP-binding cassette transporter A1 (ABCA1) expression, ABCA1-mediated cholesterol efflux, and aortic AS. Macrophage sortilin expression was upregulated by oxidized low-density lipoproteins (ox-LDLs) in both concentration- and time-dependent manners. Its expression reached the peak level when cells were incubated with 50 µg/ml ox-LDL for 24 h. Overexpression of sortilin in macrophage reduced cholesterol efflux, leading to an increase in intracellular total cholesterol, free cholesterol, and cholesterol ester. Sortilin was found to bind with ABCA1 protein and suppress macrophage ABCA1 expression, resulting in a decrease in cholesterol efflux from macrophages. The inhibitory effect of sortilin in cholesterol efflux was partially reversed by treatment with chloroquine, a lysosomal inhibitor. On the contrary, the ABCA1 protein level and ABCA1-mediated cholesterol efflux is increased by sortilin short hairpin RNA transfection. The fecal and biliary cholesterol 3H-sterol from cholesterol-laden mouse peritoneal macrophage was reduced by sortilin overexpression through lentivirus vector (LV)-sortilin in low-density lipoprotein receptor knockout mice, which was prevented by co-treatment with chloroquine. Treatment with LV-sortilin reduced plasma high-density lipoprotein and increased plasma ox-LDL levels. Accordingly, aortic lipid deposition and plaque area were exacerbated, and ABCA1 expression was reduced in mice in response to infection with LV-sortilin alone. These effects of LV-sortilin were partially reversed by chloroquine. Sortilin enhances lysosomal degradation of ABCA1 protein and suppresses ABCA1-mediated cholesterol efflux from macrophages, leading to foam cell formation and AS development.

The zonal pattern of arterial supply to the brachial plexus and its clinical significance.

PURPOSE: To provide the anatomical basis of blood supply of brachial plexus for the clinical microsurgical treatment of brachial plexus injury. METHODS: Thirteen adult anticorrosive cadaveric specimens (8 males, 5 females) were dissected in this study. 3 fresh cases (2 males, 1 female) were used to observe the zonal pattern of arteries supplying brachial plexus, and 10 cases (6 males, 4 females) were used to observe the source and distribution of the brachial plexus arteries under microscope. RESULTS: The brachial plexus is supplied by branches of the subclavian-axillary axis (SAA), and these branches anastomose each other. According to distribution feature, blood supply of the brachial plexus could be divided into three zones. The first zone was from the nerve roots of intervertebral foramina to its proximal trunks, which was supplied by the vertebral artery and the deep cervical artery. The second zone was from the distal nerve trunks of the brachial plexus, encompassing the divisions to its proximal cords, which was supplied by direct branches of the subclavian artery or by branches originating from the dorsal scapular artery. The third zone was from the distal portion of the cords to terminal branches of the brachial plexus, which was supplied by direct branches of the axillary artery. CONCLUSIONS: The zonal pattern of arterial supply to the brachial plexus is a systematic and comprehensive modality to improve anatomical basis for the clinical microsurgical treatment for brachial plexus injury.

Implications of Sortilin in Lipid Metabolism and Lipid Disorder Diseases.

The present review provides a summary of recent evidence of sortilin expression, function, and regulation and its implications in lipid metabolism and development of lipid disorder diseases. As a member of the vacuolar protein sorting 10 protein (Vps10p) receptor family, sortilin mediates intracellular trafficking of diverse endogenous or exogenous protein substrates between the trans-Golgi network (TGN) and plasma membrane compartments. Recent studies reveal that sortilin regulates the expression of lipid genes, plasma lipid level, and the development of lipid disorder diseases. Sortilin promotes atherogenesis by regulating hepatic very low density lipoprotein (VLDL) secretion and plasma lipid level and subsequently macrophage lipid accumulation. Sortilin deficiency is caused by accelerated proteasome degradation under insulin resistance conditions and is thereby implicated in the hyperlipidemia of type 2 diabetes mellitus (T2DM). Sortilin facilitates hepatic cholesterol accumulation by inhibiting hepatic cholesterol catabolism, which promotes the development of nonalcoholic fatty liver disease (NAFLD). Sortilin plays an important role in lipid metabolism and represents a promising therapeutic target for lipid disorder diseases.