Development of 3D printed electrospun vascular graft loaded with tetramethylpyrazine for reducing thrombosis and restraining aneurysmal dilatation.

Background: Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations. Methods: Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety. Results: Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed. Conclusions: The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.

Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High-Pressure Wound Environments.

The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound environments. Traditional self-gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self-gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises ε-polylysine (ε-PLL) and 4-arm polyethylene glycol succinyl succinate (4-arm-PEG-NHS) forming the hydrogel framework. Na2HPO4 functions as the "H+ sucker" to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross-linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage.

Advancing homogeneous networking principles for the development of fatigue-resistant, low-swelling and sprayable hydrogels for sealing wet, dynamic and concealed wounds in vivo.

Effective sealing of wet, dynamic and concealed wounds remains a formidable challenge in clinical practice. Sprayable hydrogel sealants are promising due to their ability to cover a wide area rapidly, but they face limitations in dynamic and moist environments. To address this issue, we have employed the principle of a homogeneous network to design a sprayable hydrogel sealant with enhanced fatigue resistance and reduced swelling. This network is formed by combining the spherical structure of lysozyme (LZM) with the orthotetrahedral structure of 4-arm-polyethylene glycol (4-arm-PEG). We have achieved exceptional sprayability by controlling the pH of the precursor solution. The homogeneous network, constructed through uniform cross-linking of amino groups in protein and 4-arm-PEG-NHS, provides the hydrogel with outstanding fatigue resistance, low swelling and sustained adhesion. In vitro testing demonstrated that it could endure 2000 cycles of underwater shearing, while in vivo experiments showed adhesion maintenance exceeding 24 h. Furthermore, the hydrogel excelled in sealing leaks and promoting ulcer healing in models including porcine cardiac hemorrhage, lung air leakage and rat oral ulcers, surpassing commonly used clinical materials. Therefore, our research presents an advanced biomaterial strategy with the potential to advance the clinical management of wet, dynamic and concealed wounds.

Bisabosqual A: A novel asparagine synthetase inhibitor suppressing the proliferation and migration of human non-small cell lung cancer A549 cells.

Asparagine synthetase (ASNS) is a crucial enzyme for the de novo biosynthesis of endogenous asparagine (Asn), and ASNS shows the positive relationship with the growth of several solid tumors. Most of ASNS inhibitors are analogs of transition-state in ASNS reaction, but their low cell permeability hinders their anticancer activity. Therefore, novel ASNS inhibitors with a new pharmacophore urgently need to be developed. In this study, we established and applied a system for in vitro screening of ASNS inhibitors, and found a promising unique bisabolane-type meroterpenoid molecule, bisabosqual A (Bis A), able to covalently modify K556 site of ASNS protein. Bis A targeted ASNS to suppress cell proliferation of human non-small cell lung cancer A549 cells and exhibited a synergistic effect with L-asparaginase (L-ASNase). Mechanistically, Bis A promoted oxidative stress and apoptosis, while inhibiting autophagy, cell migration and epithelial-mesenchymal transition (EMT), impeding cancer cell development. Moreover, Bis A induced negative feedback pathways containing the GCN2-eIF2α-ATF4, PI3K-AKT-mTORC1 and RAF-MEK-ERK axes, but combination treatment of Bis A and rapamycin/torin-1 overcame the potential drug resistance triggered by mTOR pathways. Our study demonstrates that ASNS inhibition is promising for cancer chemotherapy, and Bis A is a potential lead ASNS inhibitor for anticancer development.

A two-year retrospective study on traumatic dental injury in the primary dentition.

The aim of this study was to analyze the causes, clinical characteristics, social factors, and current status of treatment of traumatic dental injury (TDI) in the primary dentition. A retrospective analysis was performed on 144 children (213 teeth) with TDI in the primary dentition from our hospital between December 2017 and June 2020. Data were analyzed using the chi-square test and the Mann-Withney-Wilcoxon test. Boys accounted for 68.1% (98/144) and girls for 31.9% (46/144) of all 144 children with TDI in the primary dentition, with a boy-girl ratio of 2.13:1. The primary age of TDI in deciduous teeth was 2 to 4 years old, accounting for 59% of all cases. Collision with others and fall were the 2 main causes of trauma to the deciduous teeth, making up 52.1% and 44.4% of all causes, respectively. Crown fracture injury was the most common type of TDI in the primary dentition, accounting for 37% of all cases (53/144). Of the 144 cases, 17.4% (25/144) was accompanied by soft tissue laceration, while 22.2% (32/144) by swelling or contusion of tissue. Maxillary teeth (92.4%) were more vulnerable to injury than mandibular teeth (7.5%), with maxillary incisor being the most vulnerable 1 (91.5%). The percentage of children arrived at the hospital for treatment 24 hours after the injury was the highest (57.0%, 82/144). After the hospital visit, 74.3% of children received treatment for the dental trauma. In terms of the treatment modalities, extraction of the traumatized teeth (27.1%) and pulpectomy + resin filling (or preformed crown) restoration were predominant. Approximately 28.5% (41/144) of cases were reviewed within 2 years, with the proportion of children with pulpitis or periapical infection being the highest (29.3%, 12/41). Age, gender, collision, and fall are the factors linked to a higher risk of TDI in the primary dentition in children under the age of 7. Resin filling (or preformed crown) restoration and pulpectomy are effective in preserving the affected tooth and controlling infection. However, the preservation of the affected tooth and the prevention of infection may be hampered by late visits and low follow-up rates.

MiR-20a promotes osteogenic differentiation in bone marrow-derived mesenchymal stem/stromal cells and bone repair of the maxillary sinus defect model in rabbits.

Introduction: This study aimed to determine whether miR-20 promoted osteogenic differentiation in bone marrow-derived mesenchymal stem/stromal cells (BMSCs) and accelerated bone formation in the maxillary sinus bone defect model in rabbits. Methods: BMSCs were transfected with miR-20a or anti-miR-20a for 12 h, followed by detection of RUNX2, Sp7 mRNA, bone morphogenetic protein 2 (BMP2), and RUNX2 protein expression. Alkaline phosphatase (ALP) activity and Alizarin Red S staining were used to detect calcified nodule deposition. In the rabbit maxillary sinus bone defect model, miR-20a loaded with AAV and BMP2 protein were mixed with Bio-Oss bone powder for filling the bone defect. At 4 weeks and 8 weeks, bone density was detected by cone beam computed tomography (CBCT), and new bone, osteoblasts, and collagen type 1 were evaluated by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. Results: Overexpression of miR-20a enhanced the mRNA and protein levels of BMP2, RUNX2, and SP7, the activity of ALP, and the levels of matrix mineralization, whereas the levels and activity of the aforementioned factors were decreased by anti-miR-20a treatment of BMSCs. Furthermore, miR-20a significantly increased the bone density, the number of osteoblasts, and the secretion of collagen type 1 in bone defects compared with Bio-Oss bone powder in the rabbit maxillary sinus bone defect model. Conclusion: Overall, miR-20a can induce osteogenic differentiation in BMSCs and accelerate bone formation of maxillary sinus defects in rabbits.

Comparison of cephalometric measurements of the Twin Block and A6 appliances in the treatment of Class II malocclusion: a retrospective comparative cohort study.

Background: Skeletal Class II malocclusion is a common malocclusion that seriously affects patients' profile and occlusal function. The key to treatment is to use functional appliances guide the mandible forward. This study aimed to evaluate the clinical efficacy of traditional functional appliance Twin Block (TB) and invisible functional appliance (A6). Methods: In the retrospective cohort study, 46 patients with Class II Division 1 mandibular retrognathia (23 females, 23 males; mean age 13.66±4.25 years) from the Third Affiliated Hospital of Sun Yat-sen University were selected. They were divided into A6 group and TB group according to the type of appliance guided mandibular forward used in orthodontic treatment (n=23 each; average treatment time 9.82±3.52 months). Lateral cephalometric radiographs were taken before and at the end of each treatment, and paired t-test or paired rank-sum tests were performed when appropriate to detect any statistical significance at the level of α=0.05. Results: The baseline characteristics of the two groups of patients were similar. Treatment with both appliances helped correct Class II malocclusion, improve the discrepancy between the maxilla and mandible, reduce the labial inclination of the maxillary anterior teeth, and relieve the deep overbite. A comparison of the treatment effects of the TB and A6 groups showed that the A6 had a better effect when moving Point A backward, and performed better in the abduction of the anterior teeth. TB group has more advantages than A6 group in moving forward point B and improving the nasolabial angle. Conclusions: Both the A6 and TB can significantly improve Class II malocclusion. A6 showed an obvious advantage in moving Point A backward and adducting the anterior teeth, which better corrects a skeletal Class II malocclusion.

The Genetic Basis of Phosphorus Utilization Efficiency in Plants Provide New Insight into Woody Perennial Plants Improvement.

Soil nutrient restrictions are the main environmental conditions limiting plant growth, development, yield, and quality. Phosphorus (P), an essential macronutrient, is one of the most significant factors that vastly restrains the growth and development of plants. Although the total P is rich in soil, its bio-available concentration is still unable to meet the requirements of plants. To maintain P homeostasis, plants have developed lots of intricate responsive and acclimatory mechanisms at different levels, which contribute to administering the acquisition of inorganic phosphate (Pi), translocation, remobilization, and recycling of Pi. In recent years, significant advances have been made in the exploration of the utilization of P in annual plants, while the research progress in woody perennial plants is still vague. In the meanwhile, compared to annual plants, relevant reviews about P utilization in woody perennial plants are scarce. Therefore, based on the importance of P in the growth and development of plants, we briefly reviewed the latest advances on the genetic and molecular mechanisms of plants to uphold P homeostasis, P sensing, and signaling, ion transporting and metabolic regulation, and proposed the possible sustainable management strategies to fasten the P cycle in modern agriculture and new directions for future studies.

Dynamic physiological and transcriptome changes reveal a potential relationship between the circadian clock and salt stress response in Ulmus pumila.

Despite the important role the circadian clock plays in numerous critical physiological responses in plants, such as hypocotyl elongation, leaf movement, stomatal opening, flowering, and stress responses, there have been no investigations into the effect of the circadian clock on physiological and transcriptional networks under salt stress. Ulmus pumila L. has been reported to tolerate 100-150 mM NaCl treatment. We measured the diurnal variation in photosynthesis and chlorophyll fluorescence parameters and performed a time-course transcriptome analysis of 2-years-old U. pumila seedlings under salt treatment to dissect the physiological regulation and potential relationship between the circadian network and the salt stress response. Seedlings in 150 mM NaCl treatment exhibited salt-induced physiological enhancement compared to the control group. A total of 7009 differentially expressed unigenes (DEGs) were identified under salt stress, of which 16 DEGs were identified as circadian rhythm-related DEGs (crDEGs). Further analysis of dynamic expression changes revealed that DEGs involved in four crucial pathways-photosynthesis, thiamine metabolism, abscisic acid synthesis and metabolism, and the hormone-MAPK signal crosstalk pathway-are closely related to the circadian clock. Finally, we constructed a co-expression network between the circadian clock and these four crucial pathways. Our results help shed light on the molecular link between the circadian network and salt stress tolerance in U. pumila.

A Nano-Silver Loaded PVA/Keratin Hydrogel With Strong Mechanical Properties Provides Excellent Antibacterial Effect for Delayed Sternal Closure.

Delayed chest closure (DSC) is widely performed during the treatment of congenital heart diseases. However, the high prevalence of surgical site infection (SSI) in patients undergoing DSC affects prognosis negatively. Herein, we designed a suturable poly (vinyl alcohol)/keratin film loaded with silver nanoparticles (AgNPs) as an alternative material for DSC, which was named PVA/Keratin/AgNPs. The PVA/Keratin/AgNPs films exhibited significantly enhanced mechanical strength after crosslinking by sodium trimetaphosphate (STMP). These films were non-toxic, and cells proliferated with good morphology after 1 week of culture. In addition, PVA/Keratin/AgNPs films provided superior antibacterial ability, as evidenced by the eradication and lower growth rate of Staphylococcus aureus and Escherichia coli. Finally, the PVA/Keratin/AgNPs films were demonstrated to successfully cover the chest cavity temporarily and protect the chest cavity from bacterial infection. These results indicated that the PVA/Keratin/AgNPs films have great prospects to be further exploited for clinical applications in DSC.

A New Geniposidic Acid Derivative Exerts Antiaging Effects through Antioxidative Stress and Autophagy Induction.

Two compounds that can prolong the replicative lifespan of yeast, geniposidic acid (Compound 1) and geniposide (Compound 2), were isolated from Gardenia jasminoides Ellis. Compared with Compound 1, Compound 2 was different at C11 and showed better bioactivity. On this basis, seven new geniposidic derivatives (3-9) were synthesized. Geniposidic 4-isoamyl ester (8, GENI), which remarkably prolonged the replicative and chronological lifespans of K6001 yeast at 1 µM, was used as the lead compound. Autophagy and antioxidative stress were examined to clarify the antiaging mechanism of GENI. GENI increased the enzymes activities and gene expression levels of superoxide dismutase (SOD) and reduced the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) to improve the survival rate of yeast under oxidative stress. In addition, GENI did not extend the replicative lifespan of ∆sod1, ∆sod2, ∆uth1, ∆skn7, ∆cat, and ∆gpx mutants with K6001 background. The free green fluorescent protein (GFP) signal from the cleavage of GFP-Atg8 was increased by GENI. The protein level of free GFP showed a considerable increase and was time-dependent. Furthermore, GENI failed to extend the replicative lifespans of ∆atg32 and ∆atg2 yeast mutants. These results indicated that antioxidative stress and autophagy induction were involved in the antiaging effect of GENI.

Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.

Ehretiquinone from Onosma bracteatum Wall Exhibits Antiaging Effect on Yeasts and Mammals through Antioxidative Stress and Autophagy Induction.

The antiaging benzoquinone-type molecule ehretiquinone was isolated in a previous study as a leading compound from the herbal medicine Onosma bracteatum wall. This paper reports the antiaging effect and mechanism of ehretiquinone by using yeasts, mammal cells, and mice. Ehretiquinone extends not only the replicative lifespan but also the chronological lifespan of yeast and the yeast-like chronological lifespan of mammal cells. Moreover, ehretiquinone increases glutathione peroxidase, catalase, and superoxide dismutase activity and reduces reactive oxygen species and malondialdehyde (MDA) levels, contributing to the lifespan extension of the yeasts. Furthermore, ehretiquinone does not extend the replicative lifespan of Δsod1, Δsod2, Δuth1, Δskn7, Δgpx, Δcat, Δatg2, and Δatg32 mutants of yeast. Crucially, ehretiquinone induces autophagy in yeasts and mice, thereby providing significant evidence on the antiaging effects of the molecule in the mammalian level. Concomitantly, the silent information regulator 2 gene, which is known for its contributions in prolonging replicative lifespan, was confirmed to be involved in the chronological lifespan of yeasts and participates in the antiaging activity of ehretiquinone. These findings suggest that ehretiquinone shows an antiaging effect through antioxidative stress, autophagy, and histone deacetylase Sir2 regulation. Therefore, ehretiquinone is a promising molecule that could be developed as an antiaging drug or healthcare product.

Congenitally Corrected Transposition of the Great Arteries: Mid-term Outcomes of Different Surgical Strategies.

BACKGROUND: Optimal management for congenitally corrected transposition of the great arteries (ccTGA) is controversial. We applied different surgical strategies based on individual variations in our single-centered practice over 10 years, aming to describe the mid-term results. METHODS: From January 2008 to June 2021, 90 patients with ccTGA were reviewed and grouped by three different surgical strategies: 41 cases with biventricular correction as biventricular group, 11 cases with 1.5 ventricular correction as 1.5 ventricular group, and 38 cases with Fontan palliation as univentricular group. The mean age at primary surgery was 41.4 ± 22.7 months. Patients were followed for mortality, complications, reoperation, cardiac function, and valve status. RESULTS: The median follow-up period was 5.1 years (range, 1.5-12.5 years). The overall 10-year survival and freedom from reoperation rate was 86.7 and 82.4%, respectively. There were 3 early deaths and 3 mid-term deaths in the biventricular group, while 2 early deaths and 1 mid-term deaths were reported in the univentricular group. Although 1.5 ventricular group presented no death and the fewest complications, we still found similar mortality (p = 0.340) and morbidity (p = 0.670) among the three groups. The bypass time, aortic-clamp time, and ICU stay length were the longest in the biventricular group, followed by the 1.5 ventricular group (p < 0.001). However, in mid-term follow-up, biventricular and 1.5 ventricular groups both showed excellent cardiac function and obvious improvement of tricuspid regurgitation (p = 0.008 and p = 0.051, respectively). Fontan palliation provided acceptable mid-term outcomes as well, despite a lower ejection fraction. CONCLUSION: Satisfactory mid-term outcomes could be achieved for highly selected ccTGA patients using the whole spectrum of surgical techniques. Moreover, 1.5 ventricular correction, as a new emerging technique in recent years, might hold great promise in future practice.

Impact of 3D Printing on Short-Term Outcomes of Biventricular Conversion From Single Ventricular Palliation for the Complex Congenital Heart Defects.

Background: Although Fontan palliation seems to be inevitable for many patients with complex congenital heart defects (CHDs), candidates with appropriate conditions could be selected for biventricular conversion. We aimed to summarize our single-center experience in patient selection, surgical strategies, and early outcomes in biventricular conversion for the complex CHD. Methods: From April 2017 to June 2021, we reviewed 23 cases with complex CHD who underwent biventricular conversion. Patients were divided into two groups according to the development of the ventricles: balanced ventricular group (15 cases) and imbalanced ventricular group (8 cases). Early and short-term outcomes during the 30.2 months (range, 4.2-49.8 months) follow-up period were compared. Results: The overall mortality rate was 4.3% with one death case. In the balanced ventricular group, 6 cases received 3D printing for pre-operational evaluation. One case died because of heart failure in the early postoperative period. One case received reoperation due to the obstruction of the superior vena cava. In the imbalanced ventricular group, the mean left ventricular end-diastolic volume was (33.6 ± 2.1) ml/m2, the mean left ventricular end-diastolic pressure was 9.1 ± 1.9 mmHg, and 4 cases received 3D printing. No death occurred while one case implanted a pacemaker due to a third-degree atrioventricular block. The pre-operational evaluation and surgery simulation with a 3D printing model helped to reduce bypass time in the balanced group (p < 0.05), and reduced both bypass and aorta clamp time in the imbalanced group (p < 0.05). All patients presented great cardiac function in the follow-up period. Conclusion: Comprehensive evaluation, especially 3D printing technique, was conducive to finding the appropriate cases for biventricular conversion and significantly reduced surgery time. Biventricular conversion in selected patients led to promising clinical outcomes, albeit unverified long-term results.

Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress.

The budding yeast Saccharomyces cerevisiae has been used as a model organism for the basic mechanism of aging, which provides useful assay systems for measuring both replicative and chronological lifespans. In the course of our screening program for substances that extend replicative lifespan, cucurbitacin B (CuB) was found as a hit compound from a compound library, which contains cerebrosides, phenols, sesquiterpenoid, triterpenoids, and sterols isolated from natural products by our research group. Importantly, it prolonged not only the replicative lifespan but also the chronological lifespan in yeast. CuB increased ATG32 gene expression, suggesting that CuB induces autophagy. Indeed, the GFP signal generated from the cleavage of GFP-Atg8, which is a signature of autophagy, was increased upon CuB treatment. On the other hand, CuB failed to increase the chronological lifespans when either ATG2 or ATG32, essential autophagy genes, was deleted, indicating that the lifespan extension by CuB depends on autophagy induction. Furthermore, CuB significantly increased superoxide dismutase (Sod) activity and the survival rate of yeast under oxidative stress, while it decreased the amount of reactive oxygen species (ROS) and malondialdehyde (MDA) production, indicating that CuB has activity to antagonize oxidative stress. Additionally, CuB did not affect replicative lifespans of sod1, sod2, uth1, and skn7 mutants with the K6001 background, indicating that aging-related genes including SOD1, SOD2, UTH1, and SKN7 participate in the antiaging effect of CuB. These results suggest that CuB exerts antiaging activity by regulating autophagy, ROS, antioxidative ability, and aging-related genes. Finally, we discuss the possible intracellular targets of CuB based on the phenotypic comparison between the CuB and global gene deletion databases.

Structure Characterization and Action Mechanism of an Antiaging New Compound from Gastrodia elata Blume.

A new compound, bis(4-hydroxybenzyl)ether mono-ß-L-galactopyranoside (1), was isolated from the rhizome of Gastrodia elata Blume. Its structure was elucidated using extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-TOF-MS, and chemical derivatization. Compound 1 extended the replicative lifespan of K6001 and the chronological lifespan of YOM36 yeast strains. To understand the mechanism of action, oxidative stress assessment, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, catalase (CAT) and total glutathione peroxidase (GPx) activity assays, and replicative lifespan assay of sod1, sod2, uth1, and skn7 yeast mutant strains were performed. Results indicated the significant increase in the survival rate of yeast under oxidative stress after treatment with 1. ROS and MDA levels were reduced significantly. Meanwhile, the activity of CAT and GPx was significantly increased. The lifespan of sod1, sod2, uth1, and skn7 mutants of K6001 was not affected by 1. Furthermore, we investigated the gene expression related to longevity after administrating 1. The significant increase of Sir2 and reduction of Uth1 gene expression in the 1-treated group were observed. These results indicated that antioxidative stress played an important role in the antiaging effect of 1; Sir2 and Uth1 genes were involved in antiaging effects of 1.

Novel Anti-Aging Benzoquinone Derivatives from Onosma bracteatum Wall.

The aim of this study was to investigate anti-aging molecules from Onosma bracteatum Wall, a traditional medicinal plant used in the Unani and Ayurvedic systems of medicine. During bioassay-guided isolation, two known benzoquinones, allomicrophyllone (1) and ehretiquinone (2) along with three novel benzoquinones designated as ehretiquinones B-D (3-5) were isolated from O. bracteatum. Their structures were characterized by spectroscopic analysis through 1D and 2D NMR, by MS spectroscopic analysis and comparing with those reported in the literatures. The anti-aging potential of the isolated benzoquinones was evaluated through a yeast lifespan assay, and the results indicated that 1, 2, 4 and 5 significantly extended the replicative lifespan of K6001 yeast, indicating that these benzoquinones obtained from O. brateatum have the ability to be employed as a potential therapeutic agent against age-related diseases.

Antiaging of Cucurbitane Glycosides from Fruits of Momordica charantia L.

Methanol extracts of Momordica charantia L. fruits are extensively studied for their antiaging activities. A new cucurbitane-type triterpenoid (1) and nine other known compounds (2-10) were isolated, and their structures were determined according to their spectroscopic characteristics and chemical derivatization. Biological evaluation was performed on a K6001 yeast bioassay system. The results indicated that all the compounds extended the replicative lifespan of K6001 yeast significantly. Compound 9 was used to investigate the mechanism involved in the increasing of the lifespan. The results indicated that this compound significantly increases the survival rate of yeast under oxidative stress and decreases ROS level. Further study on gene expression analysis showed that compound 9 could reduce the levels of UTH1 and SKN7 and increase SOD1 and SOD2 gene expression. In addition, it could not extend the lifespan of the yeast mutants of Uth1, Skn7, Sod1, and Sod2. These results demonstrate that compound 9 exerts antiaging effects via antioxidative stress and regulation of UTH1, SKN7, SOD1, and SOD2 yeast gene expression.

MicroRNA-134 Promotes the Development of Atherosclerosis Via the ANGPTL4/LPL Pathway in Apolipoprotein E Knockout Mice.

AIMS: Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. METHODS: ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/ low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. RESULTS: Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. CONCLUSIONS: These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease.