Hydrogel Based on Riclin Cross-Linked with Polyethylene Glycol Diglycidyl Ether as a Soft Filler for Tissue Engineering.

Hydrogels composed of natural polysaccharides have been widely used as filling materials, with a growing interest in medical cosmetology and skin care. However, conventional commercial dermal fillers still have limitations, particularly in terms of mechanical performance and durability in vivo. In this study, a novel injectable and implantable hydrogel with adjustable characteristics was prepared from succinoglycan riclin by introducing PEG diglycidyl ether as a cross-linker. FTIR spectra confirmed the cross-linking reaction. The riclin hydrogels exhibited shear-thinning behavior, excellent mechanical properties, and cytocompatibility through in vitro experiments. Furthermore, when compared with subcutaneous injection of a commercial hyaluronic acid hydrogel, the riclin hydrogels showed enhanced persistence and biocompatibility in Balb/c mice after 16 weeks. These results demonstrate the great potential of the riclin-based hydrogel as an alternative to conventional commercial soft tissue fillers.

Pregnancy-induced physiological hypertrophic preconditioning attenuates pathological myocardial hypertrophy by activation of FoxO3a.

Previous studies show a woman's pregnancy is correlated with post-reproductive longevity, and nulliparity is associated with higher risk of incident heart failure, suggesting pregnancy likely exerts a cardioprotection. We previously reported a cardioprotective phenomenon termed myocardial hypertrophic preconditioning, but it is unknown whether pregnancy-induced physiological hypertrophic preconditioning (PHP) can also protect the heart against subsequent pathological hypertrophic stress. We aimed to clarify the phenomenon of PHP and its mechanisms. The pluripara mice whose pregnancy-induced physiological hypertrophy regressed and the nulliparous mice underwent angiotensin II (Ang II) infusion or transverse aortic constriction (TAC). Echocardiography, invasive left ventricular hemodynamic measurement and histological analysis were used to evaluate cardiac remodeling and function. Silencing or overexpression of Foxo3 by adeno-associated virus was used to investigate the role of FoxO3a involved in the antihypertrophic effect. Compared with nulliparous mice, pathological cardiac hypertrophy induced by Ang II infusion, or TAC was significantly attenuated and heart failure induced by TAC was markedly improved in mice with PHP. Activation of FoxO3a was significantly enhanced in the hearts of postpartum mice. FoxO3a inhibited myocardial hypertrophy by suppressing signaling pathway of phosphorylated glycogen synthase kinase-3ß (p-GSK3ß)/ß-catenin/Cyclin D1. Silencing or overexpression of Foxo3 attenuated or enhanced the anti-hypertrophic effect of PHP in mice with pathological stimulation. Our findings demonstrate that PHP confers resistance to subsequent hypertrophic stress and slows progression to heart failure through activation of FoxO3a/GSK3ß pathway.

Differences in the clinical presentation, management, and in-hospital outcomes of acute aortic dissection in patients with and without end-stage renal disease.

BACKGROUND: Few studies have evaluated the clinical presentation, management, and outcomes of patients with end-stage renal disease (ESRD) presenting with acute aortic dissection (AAD) in real-world clinical practice. Thus, this study investigated the clinical characteristics, management, and outcomes of AAD patients with ESRD. METHODS: A total of 217 patients were included. We evaluated the differences in the clinical features, management, and in-hospital outcomes of patients with and without a history of ESRD presenting with AAD. RESULTS: A history of ESRD was present in 71 of 217 patients. Patients with ESRD had atypical clinical manifestations (p < 0.001) and were more likely to be managed medically compared with patients without ESRD (p = 0.002). Hypertension and type B aortic dissection were significantly more common among patients with ESRD. Moreover, patients with ESRD had lower leucocyte and platelet counts than patients without ESRD in laboratory findings (p < 0.001). However, hospitalization days and in-hospital mortality were similar between the two groups (p > 0.05). Multivariate analysis identified Type A aortic dissection as an independent predictor of in-hospital mortality among patients without ESRD (OR, 13.68; 95% CI, 1.92 to 98.90; P = 0.006). CONCLUSIONS: This study highlights differences in the clinical characteristics, management, and outcomes of AAD patients with ESRD. These patients usually have atypical symptoms and more comorbid conditions and are managed more conservatively. However, these patients have no in-hospital survival disadvantage over those without ESRD. Further studies are needed to better understand and optimize care for patients with ESRD presenting with AAD.

Alterations in gut microbiota of abdominal aortic aneurysm mice.

BACKGROUND: The gut microbiome plays an important role in various cardiovascular diseases, such as atherosclerosis and hypertension, which are associated with abdominal aortic aneurysms (AAAs). METHODS: Here, we used 16S rRNA sequencing to explore gut microbiota in C57BL ApoE-/- mice with AAAs. A mouse model of abdominal aortic aneurysms was induced with angiotensin II (Ang II) (1000 ng/min per kg). On day 28 after the operation, fecal samples were collected and stored at - 80 °C until DNA extraction. We determined the relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding, and sequences were analyzed using a combination of mother software and UPARSE. RESULTS: We found that the gut microbiome was different between control and AAA mice. The results of correlation analysis between AAA diameter and the gut microbiome as well as LEfSe of the genera Akkermansia, Odoribacter, Helicobacter and Ruminococcus might be important in the progression of AAAs. CONCLUSIONS: AAA mice is subjected to gut microbial dysbiosis, and gut microbiota might be a potential target for further investigation.

Hemoadhican-Based Bioabsorbable Hydrogel for Preventing Postoperative Adhesions.

Postoperative peritoneal adhesions are a prevalent clinical issue following abdominal and pelvic surgery, frequently resulting in heightened personal and societal health burdens. Traditional biomedical barriers offer limited benefits because of practical challenges for doctors and their incompatibility with laparoscopic surgery. Hydrogel materials, represented by hyaluronic acid gels, are receiving increasing attention. However, existing antiadhesive gels still have limited effectiveness or carry the risk of complications in clinical applications. Herein, we developed a novel hydrogel using polysaccharide hemoadhican (HD) as the base material and polyethylene glycol diglycidyl ether (PEGDE) as the cross-linking agent. The HD hydrogels exhibit appropriate mechanical properties, injectability, and excellent cytocompatibility. We demonstrate resistance to protein adsorption and L929 fibroblast cell adhesion to the HD hydrogel. The biodegradability and efficacy against peritoneal adhesion are further evaluated in C57BL/6 mice. Our results suggest a potential strategy for anti-postoperative tissue adhesion barrier biomaterials.

Succinoglycan riclin relieves UVB-induced skin injury with anti-oxidant and anti-inflammatory properties.

Excessive UVB exposure increases the production of reactive oxygen species (ROS), which causes oxidative damage and epidermal inflammation. Previous studies have identified that the succinoglycan riclin has potent anti-inflammatory properties. The current study aims to investigate whether riclin protects against UVB-induced photodamage. In vitro, riclin demonstrated excellent moisture-preserving properties, along with antioxidant potential by scavenging superoxide anions, hydroxyl and DPPH radicals. Riclin increased Col1α1 and Col3α1 expression in NIH3T3 cells, inhibited oxidation and melanin synthesis by B16F10 cells upon UVB irradiation. In vivo, topical application of riclin effectively attenuated UVB-induced skin damage in C57BL6 mice, which was characterized by erythema, epidermal hyperplasia, hydroxyproline loss and ROS production in skin tissue. Riclin suppressed skin inflammation by the elevation of TNF-α, IL-6, IL-ß, and alleviated UVB-induced immune cell up-regulation. Moreover, treatment with a Dectin-1 inhibitor reversed the protective effect of riclin in THP-1 cells.

Identification of a miRSNP Regulatory Axis in Abdominal Aortic Aneurysm by a Network and Pathway-Based Integrative Analysis.

Abdominal aortic aneurysm (AAA) refers to local abnormal expansion of the abdominal aorta and mostly occurs in elderly men. MicroRNA (miRNA) is single-stranded RNA consisting of 18-25 nucleotides. It plays a key role in posttranscriptional gene expression and in the regulation of human functions and disease development. miRNA exerts its function mainly through the binding of complementary base pairs to the 3' regulatory region of mRNA transcripts. Therefore, miRNA-related single-nucleotide polymorphisms (miRSNPs) can affect miRNA expression and processing kinetics. miRSNPs can be classified based on their location: miRSNPs within miRNA-producing genes and miRSNPs within miRNA target genes. Increasing evidence indicates that miRSNPs play an important role in the pathogenic kinetics of cardiovascular diseases. The aim of this study was to identify potential miRNAs and integrate them into a miRSNP-based disease-related pathway network, the results of which are of great significance to the interpretation of the potential mechanisms and functions of miRSNPs in the pathogenesis of diseases.

Loss of FoxO3a prevents aortic aneurysm formation through maintenance of VSMC homeostasis.

Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. In addition, in cultured VSMCs, significant enhancement of FoxO3a expression was found during angiotensin II (Ang II)-induced VSMC phenotypic switching. In vivo, FoxO3a overexpression in C57BL/6J mice treated with Ang II increased the formation of AAAs, whereas FoxO3a knockdown exerted an inhibitory effect on AAA formation in ApoE-/- mice infused with Ang II. Mechanistically, FoxO3a overexpression significantly inhibited the expression of differentiated smooth muscle cell (SMC) markers, activated autophagy, the essential repressor of VSMC homeostasis, and promoted AAA formation. Our study revealed that FoxO3a promotes VSMC phenotypic switching to accelerate AAA formation through the P62/LC3BII autophagy signaling pathway and that therapeutic approaches that decrease FoxO3a expression may prevent AAA formation.

[Preparation of scopolamine hydrobromide nanoparticles-in-microsphere system].

This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.

Orally administered salecan ameliorates methotrexate-induced intestinal mucositis in mice.

PURPOSE: Methotrexate (MTX) is a widely used cancer chemotherapy agent. The efficacy of MTX is often limited by serious side effects, such as intestinal mucositis. The aim of this study was to evaluate the protective effect of water-soluble ß-glucan salecan on MTX-induced intestinal toxicity in mice. METHODS: Intestinal mucositis was induced in C57BL/6 mice by intraperitoneal injection of MTX for two consecutive days. Mice were orally administrated with saline or salecan for 6 days before MTX injection and continued to the end of the study. Several histological and biochemical parameters were measured in the jejunum. RESULTS: Orally administration of salecan improved the severity of intestinal mucositis in a dose-dependent manner, as evidenced by the well-maintained mucosal architecture and body weight in salecan-treated groups. Salecan treatment inhibited MTX-induced oxidative stress and effectively scavenged free radicals both in vitro and in vivo. Metabolomics analysis revealed that salecan treatment reversed the intestinal metabolic profiling changes in mice with MTX-induced mucositis. Salecan treatment modulated the innate immunity through the regulation of TLR and Dectin1 expression in the jejunum, thus protecting mice from MTX-induced intestinal damage. CONCLUSIONS: Salecan has potential advantages in the treatment of MTX-induced intestinal mucositis, and its protective effect is mainly attributed to its antioxidant and immunomodulatory properties.

Pancreatic lipase-related protein 2 is responsible for the increased hepatic retinyl ester hydrolase activity in vitamin A-deficient mice.

The formation and hydrolysis of hepatic retinyl esters (RE) is a key process in maintaining serum retinol homeostasis. During vitamin A deficiency, the activity of RE hydrolases (REH) in liver increases to cope with the reduced dietary vitamin A intake. However, it remains unclear which REH is the main enzyme responsible for RE hydrolysis in the liver under physiological conditions. Our previous studies have shown that pancreatic lipase-related protein 2 (PLRP2) is conditionally expressed in the liver and may be involved in the hydrolysis of hepatic RE. In the current study, we generated Plrp2-/- mice using transcription activator-like effector nuclease technology to investigate the role of PLRP2 in the metabolism of hepatic RE. Compared with the mice fed normal diet, the hepatic REH activity of wild-type (WT) mice fed vitamin A-deficient diet (VAD) increased significantly, while this activity did not increase in Plrp2-/- mice fed VAD. Plrp2-/- mice showed higher residual RE content in liver and lower serum retinol level, compared with WT mice fed VAD. Hepatic metabolic profiling from 1 H NMR-based metabolomics suggested that Plrp2-/- mice were more sensitive to VAD. Docking analysis and enzyme activity assay revealed that retinyl palmitate was the substrate with higher affinity for PLRP2. Our results indicate that Plrp2 can be activated in the liver and is responsible for the increased REH activity in the liver of mice fed VAD.

Effect of anesthesia on cognitive status and MMP-2 expression in rats.

OBJECTIVE: To investigate the effect of anesthesia on the cognitive status damage and MMP-2 expression in rats. METHODS: A total of 120 healthy rats were selected and randomly divided into the control group, CF3-CH(OCH2F)-CF3 (Sevoflurane) group and CF3-CH2-O-CHF-CF3 group (Sevoflurane) (n=40). After training for 3 d by the Morris water maze, the control group were injected with fentanyl for analgesia, the CF3-CH(OCH2F)-CF3 group and the CF3-CH2-O-CHF-CF3 group were anesthesia with CF3-CH (OCH2F)-CF3 and CF3-CH2-O-CHF-CF3 on the basis of fentanyl, then rats in three groups underwent open surgery and suture conventional incision. Morris water maze was used to measure the rats' cognitive ability in three groups on the 1st d, 3rd d, 5th d and 7th d, and the brain tissue MMP-2 expression was detected. RESULTS: After 1 d/7 d of the surgery, Morris water maze performance and MMP-2 expression were not significantly different among three groups (P>0.05); After 3 d/5 d of the surgery, compared with the control group, the Morris water maze test result was significantly worsened, MMP-2 expression levels were significantly increased (P<0.05); After 3 d/5 d of the surgery, compared with the CF3-CH2-O-CHF-CF3 group, Morris water maze test result of CF3-CH(OCH2F)-CF3 group was significantly worsened, MMP-2 expression levels were significantly increased (P<0.05). CONCLUSIONS: Anesthesia can cause some injury on cognitive status, different anesthetic drugs may cause different injury, and the cognitive status injury is related to the MMP-2 expression.