Accurate Recognition of Vascular Lumen Region from 2D Ultrasound Cine Loops for Bubble Detection.

BACKGROUND: Accurate identification of vascular lumen region founded the base of bubble detection and bubble grading, which played a significant role in the detection of vascular gas emboli for the diagnosis of decompression sickness. OBJECTIVES: To assist in the detection of vascular bubbles, it is crucial to develop an automatic algorithm that could identify vascular lumen areas in ultrasound videos with the interference of bubble presence. METHODS: This article proposed an automated vascular lumen region recognition (VLRR) algorithm that could sketch the accurate boundary between vessel lumen and tissues from dynamic 2D ultrasound videos. It adopts 2D ultrasound videos of the lumen area as input and outputs the frames with circled vascular lumen boundary of the videos. Normalized cross-correlation method, distance transform technique, and region growing technique were adopted in this algorithm. Results A double-blind test was carried out to test the recognition accuracy of the algorithm on 180 samples in the images of 6 different grades of bubble videos, during which, intersection over union and pixel accuracy were adopted as evaluation metrics. The average IOU on the images of different bubble grades reached 0.76. The mean PA on 6 of the images of bubble grades reached 0.82. CONCLUSION: It is concluded that the proposed method could identify the vascular lumen with high accuracy, potentially applicable to assist clinicians in the measurement of the severity of vascular gas emboli in clinics.

LRRK2 correlates with macrophage infiltration in pan-cancer.

Leucine-rich repeat kinase2 (LRRK2) influences the host immune responses and correlates with the pathogenesis of inflammation, cancer as well as Parkinson' Disease. Herein, we explored the oncogenic role of LRRK2 at pan-cancer level and validated the analysis by single cell RNA-sequencing and in-vitro experiments. As a result, LRRK2 significantly correlated with the survival events. Specifically, LRRK2 increased the risk of Low-Grade Glioma whereas improved the survival probability of patients with Skin Cutaneous Melanoma. Gene set enrichment analysis demonstrated the involvement of LRRK2 in the host immune responses. Within the tumor microenvironment, LRRK2 was positively associated with the recruitment of macrophages. Furthermore, scRNA-seq and co-culture experiments demonstrated that LRRK2 deficiency impaired macrophage functions, and influenced the neoplastic progression in a cancer type-specific manner. Therefore, the present study provided a therapeutic strategy for LGG based on the interference with LRRK2 expression and activity to prevent macrophage recruitment and promote tumor eradication.

Network Pharmacology-Based Validation of the Efficacy of Huiyangjiuji Decoction in the Treatment of Experimental Colitis.

Ulcerative colitis (UC) is the major type of inflammatory bowel disease (IBD) characterized by an overactive immune responses and destruction of the colorectal epithelium with intricate pathological factors. In China, Huiyangjiuji decoction (HYJJ) has been widely administered against inflammation, but the underlying mechanical mechanisms are not known. A murine model of colitis was established by orally feeding 4% dextran sodium sulfate for 5 days. Intestinal organoids (IOs) were treated with TNFα (Tumor necrosis factor-α) as an ex-vivo UC model. A scratch assay combined with a co-culture system that incubated murine epithelial cell line (IEC-6) with macrophages (Mφs) was utilized to assess epithelial recovery under inflammatory conditions. Network pharmacology analysis was performed to elucidate the mechanism of HYJJ decoction. In the present study, we confirmed that HYJJ considerably alleviated of DSS-induced colitis, as evidenced by the improved intestinal injury and fecal albumin, as well as feces blood. Network pharmacology analysis identified the active components in HYJJ formula, and KEGG enrichment analysis indicated that HYJJ-target genes were enriched in pathogen-induced infections, cancer-related as well as inflammatory pathways. Consistently, RNA-sequencing demonstrated that HYJJ treated inhibited cytokine-cytokine interaction, IBD as well as TNF signaling pathways, confirming the anti-inflammatory and anti-neoplastic role of HYJJ decoction. In-vitro experimental evidence confirmed the suppression of pro-interleukins by HYJJ, including IL-2, IL-10 and IL-12. Moreover, the contribution of HYJJ to mucosal healing was corroborated by ex-vivo experiments, in which HYJJ rescued TNFα-compromised IOs functions, i.e., elevated mitochondrial stress (MOS) and impaired regeneration capacity. IEC-6 cells co-culture with Mφs from HYJJ-treated experimental colitis mice showed an improved migration capacity as compared to those incubated with Mφs from untreated colitis mice. We conclude that HYJJ re-establishes homeostasis of the gut epithelium during colitis by suppressing inflammation and orchestrating cytokines interaction.

ACE2 contributes to the maintenance of mouse epithelial barrier function.

BACKGROUND: The whole world was hit hard by the coronavirus disease-19 (COVID-19). Given that angiotensin I converting enzyme 2 (ACE2) is the viral entry molecule, understanding ACE2 has become a major focus of current COVID-19 research. ACE2 is highly expressed in the gut, but its role has not been fully understood and thus COVID-19 treatments intending to downregulate ACE2 level may cause untoward side effects. Gaining insight into the functions of ACE2 in gut homeostasis therefore merits closer examination, and is beneficial to find potential therapeutic alternatives for COVID-19. METHODS: We took advantage of Ace2 knockout out mice and isolated intestinal organoids to examine the role of ACE2 in intestinal stemness. Inflammatory bowel disease (IBD) mouse model was established by 4% dextran sodium sulfate. LGR5 and KI67 levels were quantitated to reflect the virtue of intestinal stem cells (ISCs). FITC-dextran 4 (FD-4) assay was used to assess intestinal barrier function. RESULTS: Western blotting identified the expression of ACE2 in colon, which was consistent with the results of immunofluorescence and RT-PCR. Moreover, Ace2-/- organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2-/- organoids was markedly increased compared with ace2+/+ organoids. Collectively, ace2-/- mice were more susceptible than ace2+/+ mice to IBD, including earlier bloody stool, undermined intestinal architecture and more pronounced weight loss. CONCLUSIONS: Our data reveal that ACE2 contributes to the proliferation of intestinal stem cells and hence orchestrates the mucosal homeostasis.

lncRNA-SNHG14 Promotes Atherosclerosis by Regulating RORα Expression through Sponge miR-19a-3p.

Coronary heart disease (CHD) is the most common cardiovascular disease with high prevalence, disability, and mortality. The balance between proliferation and apoptosis of vascular smooth muscle cells (VSMCs) plays a key role in the initiation of atherosclerosis. In this study, we found a significant decrease in the expression of lncRNA-SNHG14 in atherosclerotic plaque tissues of ApoE-/- mice. Overexpression of lncRNA-SNHG14 can inhibit VSMC proliferation while promoting apoptosis. There is a potential reciprocal regulatory relationship between lncRNASNHG14 and miR-19a-3p, which inhibit each other's expression in vascular smooth muscle cells. In addition, the luciferase reporter gene analysis results showed that there was a direct interaction between miR-19a-3p and the 3'UTR of RORα. The results of qRT-PCR showed that the level of RORα mRNA was significantly increased in the aortas treated with miR-19a-3p and SNHG14 compared with that treated with miR-19a-3p alone. In conclusion, we demonstrated that lncRNA-SNHG14 regulates the apoptosis/proliferation balance of VSMCs in atherosclerosis.

A bidirectional effect of Rac1 inhibition-Protects radiation-induced intestinal injury while inhibits tumor.

AIMS: To investigate whether Rac1 inhibition can alleviate radiation-induced intestinal injury (RIII), meanwhile exist no protection on tumors. MATERIALS AND METHODS: Rac1 inhibition was achieved by its specific inhibitor, NSC23766. Mice were pretreated with different intraperitoneal injections, which were normal saline for NS group (N = 9), and 2.5 mg/kg and 5 mg/kg of NSC23766 for Low-Dose group (N = 9) and High-Dose group (N = 9), respectively. After total body irritation (10Gy), small intestinal tissues were collected for Hematoxylin-Eosin (H&E) staining and Terminal-deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL). Intestinal epithelial and tumor cell lines, namely MODE-k and CT-26, were used to further study the role of Rac1 inhibition on radiation damage. Flow cytometry was used to detect changes in reactive oxygen species production, cell cycles and mitochondrial membrane potential, the latter was also checked by fluorescence microscope. Changes of protein-expression associated with apoptosis and cell cycles were detected by Western blotting to explain the possible molecular mechanism. KEY FINDINGS: Height of intestine villi and depth of crypt were higher (P < 0.01) and apoptosis ratio lower (P < 0.01) in High-Dose group compared with those in NS group. After radiation, Rac1 inhibition pre-treatment improved the vitality (P < 0.01) and reduced the apoptosis (P < 0.01) in MODE-k while yielded opposite results in CT-26, and reduced ROS production of MODE-k (P < 0.01) while had little effect on that of CT-26. Rac1 inhibition differently affected the cell cycles of normal cells and that of tumor cells. SIGNIFICANCE: Inhibition of Rac1 could alleviate RIII, meanwhile assist the killing effect of radiation on tumor cells.

Dietary cholesterol alters memory and synaptic structural plasticity in young rat brain.

Cholesterol plays an important role in synaptic plasticity, learning and memory. To better explore how dietary cholesterol contributes to learning and memory and the related changes in synaptic structural plasticity, rats were categorized into a regular diet (RD) group and a cholesterol-enriched diet (CD) group, and were fed with respective diet for 2 months. Dietary cholesterol impacts on learning and memory, hippocampal synaptic ultrastructure, expression levels of postsynaptic density-95 (PSD-95), synaptophysin (SYP) and cannabinoid receptor type 1 (CB1R) were investigated. We found CD rats had better performances in learning and memory using Morris water maze and object recognition test than RD rats. The memory improvement was accompanied with alterations of synaptic ultrastructure in the CA1 area of the hippocampus evaluated by electron microscopy, enhanced immunoreactivity of SYP, a presynaptic marker in hippocampus detected by immunocytochemistry, as well as increased levels of PSD-95, SYP and decreased level of CB1R in brains of CD rats determined by Western blot. Taken together, the results suggest that the improvement of learning and memory abilities of the young adult rats induced by dietary cholesterol may be linked with changes in synaptic structural plasticity in the brain.

[Effect of low density lipoprotein oxidizing in hyperlipidemia rats after treating with tetrahydrobiopterin].

OBJECTIVE: To explore the oxidative modification effect and its mechanism of low density lipoprotein (LDL) in hyperlipidemia (HL) rats after treating with tetrahydrobiopterin (BH4). METHODS: Fifty four 8-week-old male Wistar rats were used, these 54 rats were randomly divided into control group, high fat diet group (HL group), high fat diet and injected BH4 group (HL + BH4 group), and 18 in each group. The BH4 levels of blood fats and blood serum and its metabolites, the aortic reactive oxygen species, the end product malondialdehyde (MDA) and the LDL oxidation level were all determined by killing 6 experimental rats in each group at the first 8, 16, and 24 weeks of age respectively. RESULTS: Treating with BH4 after 8 and 16 weeks, there was no significant difference in serum lipids among three groups (P > 0. 05); but ROS and MDA decreased significantly (P < 0.01); compared with control and HL groups, the BH4 level of HL + BH4 group increased a lot (P < 0.01); compared with control group, the BH4 content reduced obviously in aortic homogenate of HL group (P < 0.01), but the total petrin levels (TB = BH4 + BH2 + B) had no significant difference (P > 0.05); the serum TBARS formation increased gradually with the increase of week-ages, but compared with HL group, the serum TBARS formation of HL + BH4 group reduced significantly (P < 0. 01). CONCLUSION: Treating with BH4 can reduced the LDL oxidation, the mechanism may be related to the correct of NOS uncoupling, the reduce of ROS generation and the decrease of LDL lipid peroxidation.

[Lipid peroxidation and biomechanical properties of artery in hyperlipemia rats after treating with tetrahydrobiopterin].

OBJECTIVE: To explore the effect of the level of lipid peroxidation and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in thoracic aorta of hyperlipemia (HL) rats. METHODS: HL rats were given BH4 chronically. The opening angle in the zero-stress state and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image 8, 16, and 24 week-old respectively. RESULTS: Treating with BH4 chronically from 8 week-old in HL rats, there was a significant increase in the zero-stress state of opening angle of thoracic aorta. The P-D curve of mesenteric artery moved upward. CONCLUSION: Treating with BH4 prevented the structure and function of artery from abnormal changing, and attenuated lipid peroxidation in HL rats.

[Biomechanical properties of artery in spontaneously hypertensive rats after treating with tetrahydrobiopterin].

AIM: To explore the effect of remodeling and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in spontaneously hypertensive rats. METHODS: The spontaneously hypertensive rat(SHR) were given with BH4 chronically. The opening angle in the zero-stress state , wall-to-lumen area ratios (W/L) of thoracic aorta and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image analysis in 4, 16, and 26 week-old respectively. RESULTS: Treating with BH4 chronically from 4 weeks-old in SHR, there was a significant decrease in morphometric parameters of the thoracic aorta and an increase in the zero-stress state of opening angle of elastic artery. The P-D curve of mesenteric artery moved upward. CONCLUSION: Treating with BH4 prevented the structure and function of artery from abnormal changing, including to attenuate the resistant vascular hypertrophy and recover the vascular elasticity and expansibility.