Salt Restriction and Angiotensin-Converting Enzyme Inhibitor Improve the Responsiveness of the Small Artery in Salt-Sensitive Hypertension.

For salt-sensitive hypertension (SSH), salt restriction and angiotensin-converting enzyme (ACE) inhibitors are essential treatments, but their effect on the function of resistance arteries is unclear. Here, we present an intravital study to detect the effect of salt restriction and ACE inhibitors on the function of the mesenteric small artery (MSA) in SSH. Dahl salt-sensitive rats were randomized into the following groups: ACE inhibitor gavage, salt restriction, ACE inhibitor combined with salt restriction, and high-salt diet. After a 12-week intervention, the mesenteric vessels maintained their perfusion in vivo, and the changes in the diameter and blood perfusion of the MSAs to norepinephrine (NE) and acetylcholine (ACh) were detected. Switching from a high-salt diet to a low-salt diet (i.e., salt restriction) attenuated the vasoconstriction of the MSAs to NE and promoted the vasodilatation to ACh, while ACE inhibitor improved the vasodilatation more obviously. Pathologically, changes in local ACE, AT1R, and eNOS expression were involved in these processes induced by a high-salt diet. Our study suggests that salt restriction and ACE inhibitor treatment improve high salt intake-induced MSA dysfunction in SSH, and salt restriction is a feasible and effective treatment. Our findings may provide a scientific basis for the treatment of hypertension.

High Sodium Intake Impairs Small Artery Vasoreactivity in vivo in Dahl Salt-Sensitive Rats.

The effects of high sodium intake on the functionality of resistance arteries have been repeatedly studied in vitro, but no study has focused on salt-sensitive hypertension in vivo. We studied the in vivo reactivity of mesenteric small arteries (MSAs) to vasoactive agents in Dahl salt-sensitive (DS) rats with various sodium diets. Twenty-four male DS rats were randomized into 3 groups: LS (0.3% NaCl diet), NS (0.6% NaCl diet), and HS (8% NaCl diet). After a 12-week intervention, the diameter changes of the MSAs after noradrenaline (NA) and acetylcholine (ACh) exposure were detected by a microscope, and changes in blood perfusion through the MSAs were measured by full-field laser perfusion imaging. HS enhanced the constrictive response of the MSAs to NA and attenuated the relaxing response to ACh. Low sodium intake reduced the response of the MSAs to NA and promoted ACh-induced vasodilatation. HS also aggravated NA-induced blood perfusion reduction and impaired ACh-induced hyperperfusion of the MSAs. Pathologically, HS was associated with arteriolar structural damage and fibrosis of the MSAs. We conclude that sodium intake affects the responsiveness of the MSAs to vasoactive agents in DS rats and might play important roles in modulating blood pressure in hypertensive individuals.

The function of guanylate binding protein 3 (GBP3) in human cancers by pan-cancer bioinformatics.

As a guanylate binding protein (GBPs) member, GBP3 is immune-associated and may participate in oncogenesis and cancer therapy. Since little has been reported on GBP3 in this field, we provide pan-cancer bioinformatics to investigate the role of GBP3 in human cancers. The GBP3 expression, related clinical outcomes, immune infiltrates, potential mechanisms and mutations were conducted using tools including TIMER2.0, GEPIA2.0, SRING, DAVID and cBioPortal. Results showed an increased risk of high GBP3 in Brain Lower Grade Glioma (LGG) and Lung Squamous Cell Carcinoma (LUSC) and a decreased risk of GBP3 in Sarcoma (SARC) and Skin Cutaneous Melanoma (SKCM) (p ≤ 0.05). GBP3 was negatively correlated with CAFs in Esophageal Adenocarcinoma (ESCA) and positively correlated with CAFs in LGG, LUSC and TGCG (p ≤ 0.05). In addition, GBP3 was positively correlated with CD8+ T cells in Bladder Urothelial Carcinoma (BLCA), Cervical Squamous Cell Carcinoma (CESC), Kidney Renal Clear Cell Carcinoma (KIRC), SARC, SKCM, SKCM-Metastasis and Uveal Melanoma (UVM) (p ≤ 0.05). Potentially, GBP3 may participate in the homeostasis between immune and adaptive immunity in cancers. Moreover, the most frequent mutation sites of GBP3 in cancers are R151Q/* and K380N. This study would provide new insight into cancer prognosis and therapy.

A nitric oxide responsive AIE probe for detecting the progression of osteoarthritis.

Nitric oxide (NO) is reported to be elevated in osteoarthritis (OA) both in vitro and in vivo and may be adopted to develop fluorescent probes for detecting the progression of OA. Here we report a nitric oxide responsive aggregation induced emission (AIE) probe TPE-2NHCOCH2CH2-(PEG)24-NH-Diacerein, which is derived from tetraphenylethene (TPE) modified with the hydrophilic group long poly(ethylene glycol) chain and an anti-inflammatory drug diacerein. o-Phenylenediamine within its structure can react with NO to form benzotriazole and emit fluorescence. The results show that the NO-responsive AIE probe can smartly monitor the progression of OA with the change of fluorescence intensity in vitro and in vivo. This study may provide a new development direction for early OA monitoring in clinics.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

PURPOSE: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. METHODS: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). RESULTS: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. CONCLUSIONS: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

The effects of cigarette smoking and smoking cessation on high-density lipoprotein functions: implications for coronary artery disease.

BACKGROUND: Smoking cessation was associated with improved prognosis of coronary artery disease. This study was designed to investigate the effect of smoking cessation on high-density lipoprotein functionality in coronary artery disease patients. METHODS: In this prospective, randomized and parallel controlled study, coronary artery disease smokers ( n = 28) and healthy smokers ( n = 30) were divided into smoking cessation group and continuous smoking group, respectively. Blood samples were collected before and after three-month smoking cessation. Plasma high-density lipoprotein was isolated by density gradient centrifugation. The ability of high-density lipoprotein against copper-induced oxidation of lipoprotein was determined to evaluate the antioxidative property of high-density lipoprotein, and the macrophage migration inhibited by high-density lipoprotein was tested to identify the antichemotactic property of high-density lipoprotein. High-density lipoprotein-induced macrophage cholesterol efflux was measured by fluorescence spectrometry using NBD cholesterol analogue. Healthy non-smoking volunteers were enrolled as the baseline control. RESULTS: The baseline antioxidative, antichemotactic ability of high-density lipoprotein and high-density lipoprotein-induced cellular cholesterol efflux in coronary artery disease smokers and healthy smokers were significantly attenuated when compared with those in healthy non-smokers. After three-month smoking cessation, both the antioxidative ability and antichemotactic ability of high-density lipoprotein were improved significantly in coronary artery disease smokers. However, high-density lipoprotein-induced cellular cholesterol efflux was not increased by smoking cessation. In in vitro experiments, carbon monoxide reduced the antioxidative ability and nicotine enhanced the antichemotactic ability of high-density lipoprotein. CONCLUSIONS: Smoking cessation is an effective measure to improve high-density lipoprotein functions in coronary artery disease smokers. Our study re-emphasizes the importance of smoking cessation in the secondary prevention of coronary artery disease.

Roles of extracellular polymeric substances in uranium immobilization by anaerobic sludge.

The specific roles of extracellular polymeric substances (EPS) and how factors influenced EPS's roles during U(VI) immobilization are still unclear. In this study, high content of U with the main form of nanoparticles was detected in EPS, accounting for 10-42% of total U(VI) removal. EPS might be utilized as energy source or even as electron donors when external carbon source was unavailable. The influencing degree of each experimental parameter to uranium (U) removal process was elucidated. The influential priority to U(IV)/U(VI) ratios in sludge was as follows: acetate, U(VI), and nitrate. The influential priority to total EPS contents was as follows: U(VI), nitrate and acetate. The complex interaction mechanism between U(VI) and EPS in the U immobilization process was proposed, which might involve three ways including biosorption, bioreduction and bioprecipitation. These results indicate important and various roles of EPS in U(VI) immobilization.

Identification of differential protein-coding gene expressions in early phase lung adenocarcinoma.

BACKGROUND: The diagnosis of early phase lung adenocarcinoma (LADC) is associated with therapeutic strategy, effect, and survival time. However, the sensitive biomarkers of early phase LADC are still unclear. This study aimed to identify protein-coding genes that can be used as biomarkers of early stage LADC. METHODS: Gene microarray analysis was performed to identify key hub genes that show different expression in lung adenocarcinoma compared to normal tissues. The microarray data of lung adenocarcinoma in stages IA, IB, IIA, IIB, and normal tissues (GSE10072) were downloaded from a free online database, Gene Expression Omnibus (GEO). RESULTS: A total of 572 differentially expressed genes (DEGs) were identified between early phase lung adenocarcinoma and normal tissues using R software. Database for Annotation, Visualization and Integrated Discovery online tools were used to obtain Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes was used to analyze DEGs. Cytoscape software was used to express the protein-protein interaction network. We found that some cancer-related Gene Ontology terms and pathways (e.g. cell adhesion, cell surface receptor signaling pathway, PI3K-Akt signaling pathway) were significantly enriched in DEGs. CONCLUSION: Protein-coding genes JUN, FYN, CAV1, and SFN may play vital roles in the progress of early-stage lung adenocarcinoma. Consequently, through bioinformatics analysis, the key genes could be established to provide more potential references for the therapeutic targets of lung adenocarcinoma.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

[Predicting the dispersal routes of alpine plant Pedicularis longiflora (Orobanchaceae) based on GIS and species distribution models].

Pedicularis longiflora experienced extensive populations' expansion in Quaternary, but the dispersal corridors were still unclear. According to the distribution patterns of haplotypes based on chloroplast DNA variation, the dispersal routes were predicted using species distribution models (MXENT) and the least-cost path method. Two possible dispersal routes from the southeastern part of Tibetan Plateau (TP) to interior were identified. The populations of East Himalayas-Hengduan Mountains region expanded to the western part of TP along with the Yarlung Zangbo River valley and the lower altitudes of the north slope of Himalayas. The expansion trend was also proved by SDMs based on two historical periods containing the Last Interglacial and the Last Glacial Maximum. In conclusion, identification of dispersal routes is significant to the evolutionary history of alpine plants and the protection of special species in TP.