Anti-skin aging effect of sea buckthorn proanthocyanidins in D-galactose-induced aging mice.

Oxidative stress in skin cells caused by changes in the external environment is one of the principal causes of skin aging. Sea buckthorn proanthocyanidins (SBPs) have good free radical scavenging ability. We established a senescence model by injecting 500 mg/kg D-galactose into the dorsal necks of mice, and then different doses of SBP (25, 50, and 100 mg/kg) were gavaged to explore the effects of SBP on the skin tissues of senescent mice and elucidate the related mechanism of action. The results reveal that SBP can alleviate the skin aging phenomenon caused by D-galactose-induced aging. It can also enhance the total antioxidant capacity in the body, thereby strengthening the body's antioxidant defense capability. In addition, SBP can effectively improve skin aging by regulating the TGF-ß1/Smads pathway and MMPs/TIMP system, increasing the relative content of Col I and tropoelastin, further maintaining the stability of collagen fiber and elastic fiber structure. These results will provide the development and production of the antioxidant function of cosmetics and health products, providing a new train of thought.

Anti-Aging Effect and Mechanism of Proanthocyanidins Extracted from Sea buckthorn on Hydrogen Peroxide-Induced Aging Human Skin Fibroblasts.

Oxidative stress is the leading cause of skin aging damage. Excessive accumulation of reactive oxygen species (ROS) in cells induced by hydrogen peroxide (H2O2) triggers a decrease in collagen synthesis and an increase in collagen degradation, which are biomarkers of skin aging. We evaluated the potential protective mechanism of Sea buckthorn proanthocyanidins (SBP) against the oxidative stress-induced skin aging process from multiple aspects. We treated human skin fibroblasts (HSFs) with 300 µmoL/L of H2O2 for 24 h, followed by 25, 50, and 100 µg/mL of SBP for 24 h. The results showed that SBP could enhance the activities of superoxide dismutase (SOD) and glutathione (GSH), effectively remove excess ROS, and significantly improve the changes in cell morphology and viability caused by excessive ROS in skin cells. In addition, SBP could promote the synthesis of Col I in aging HSFs through the TGF-ß1/Smads pathway and inhibit the degradation of Col I by regulating the MMPs/TIMPs system, thereby maintaining the stability of the ECM structure to achieve anti-aging purposes. Finally, we studied the migration ability of SBP, and the results showed that 100 µg/mL of SBP was most conducive to the cell migration of senescent cells, laying a foundation for follow-up animal experiments. These results will increase the application value of SBP in the cosmetic and antioxidative functional food industries.

Extraction and characterization of a pectin from sea buckthorn peel.

Sea buckthorn peel is the by-product of the sea buckthorn processing, which contains many bioactive compounds. In this paper, sea buckthorn high methoxyl pectin (SBHMP) was obtained, with a yield of 8% and a light-colored. The SBHMP was a high methoxyl with a degree of esterification of 57.75% and uronic acid content of 65.35%. The structural and morphological characterization of SBHMP were analyzed by high-performance liquid chromatography, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Results showed that SBHMP presented a sheet and layered stacked morphological, and was mainly composed of galacturonic acid, arabinose, galactose, rhamnose, and mannose, which indicated that SBHMP mainly consisted of homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) type pectin polysaccharides. In addition, SBHMP also presented significant gel, thickening, and emulsifying properties. The results exhibited that SBHMP could form jelly-like gels under acid and high sucrose conditions, presenting a shear-thinning behavior and increasing apparent viscosity with the enhancement of pectin and sucrose contents. Besides, SBHMP could form oil-in-water emulsions with pectin concentrations of 1.0-3.0%. When the SBHMP concentrations were 2.0 and 3.0%, the emulsions were stable during 7 days of storage. Findings in this paper demonstrated the potential of SBHMP to be a food thickener and emulsifier and support the in-depth utilization of sea buckthorn by-products.

Sea Buckthorn Proanthocyanidins are the Protective Agent of Mitochondrial Function in Macrophages Under Oxidative Stress.

Sea buckthorn proanthocyanidins (SBP) are the most important antioxidant components of sea buckthorn, which are widely used in functional foods and cosmetics. Studies have shown that SBP have significant protective effects on macrophages against oxidative stress induced by hydrogen peroxide (H2O2). However, the mechanism remains uncertain. In the present study, we explored the effects of SBP on mitochondrial function and the mechanism of their protective effects against oxidative stress in cells. Our results showed that SBP could increase mitochondrial membrane potential, inhibit mPTP opening, reduce mitochondrial swelling, and enhance mitochondrial synthesis and metabolism. Thus, they alleviated oxidative damage and protected the cells against mitochondrial function. Western blot analysis showed that SBP had a protective effect on RAW264.7 cells by activating the AMPK-PGC1α-Nrf2 pathway. These results showed that SBP alleviated mitochondrial damage and dysfunction caused by oxidative stress. This study revealed the mechanism of SBP in reducing oxidative damage and provided a theoretical basis for further research on natural bioactive compounds to exert antioxidant activity and prevent arteriosclerosis and other diseases.

Regulatory Effect of Sea-Buckthorn Procyanidins on Oxidative Injury HUVECs.

As society develops and aging populations increase, the incidence of arteriosclerosis, a seriously harmful cardiovascular disease (CVD) which mostly results from endothelial cellular oxidative damage, has continuously risen. Procyanidins from sea-buckthorn is a powerful antioxidant, although its protective effect on the cardiovascular system is not yet clearly understand. In this study, oxidative damaged HUVECs induced by palmitate acid (PA) were used as a model and the regulatory effect of procyanidins from sea-buckthorn (SBP) on HUVECs were investigated. The results showed SBP can be used for 12 h by HUVECs and had no detective cytotoxicity to them under 400 µg/L. Also, different concentrations of SBP can increase mitochondrial membrane potential and NO level and decrease LDH leakage in a dose-effect relationship, indicating SBP can improve oxidative damage. In addition, western blots and qPCR results showed SBP regulation on oxidative injured HUVECs is probably through p38MAPK/NF-κB signal pathway. This study revealed the molecular mechanism of procyanidins in decreasing endothelial oxidative damage, providing a theoretical foundation for further research on natural bioactive compounds to exert antioxidant activity in the body and prevent and improve cardiovascular diseases.

Composition analysis and antioxidant activity evaluation of a high purity oligomeric procyanidin prepared from sea buckthorn by a green method.

Procyanidin is an important polyphenol for its health-promoting properties, however, the study of procyanidin in sea buckthorn was limited. In this paper, sea buckthorn procyanidin (SBP) was obtained through a green isolation and enrichment technique with an extraction rate and purity of 9.1% and 91.5%. The structure of SBP was analyzed using Ultraviolet-visible spectroscopy (UV-vis), Fourier-transform infrared spectroscopy (FT-IR), and liquid chromatography-mass spectrometry (LC-MS/MS). The results show that SBP is an oligomeric procyanidin, mainly composed of (-)-epicatechin gallate, procyanidin B, (+)-gallocatechin-(+)-catechin, and (+)-gallocatechin dimer. SBP showed superior scavenging capacity on free radicals. Furthermore, the cleaning rate of the ABTS radical was 4.8 times higher than vitamin C at the same concentration. Moreover, SBP combined with vitamin C presented potent synergistic antioxidants with combined index values below 0.3 with concentration rates from 5:5 to 2:8. SBP also provided significant protection against oxidative stress caused by hydrogen peroxide (H2O2) on RAW264.7 cells. These findings prove the potential of SBP as a natural antioxidant in food additives and support the in-depth development of sea buckthorn resources.

Natural variants suppress mutations in hundreds of essential genes.

The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, and lethal in another. The extent to which mutant phenotypes are malleable, the architecture of modifiers and the identities of causal genes remain largely unknown. Here, we measure the fitness effects of ~ 1,100 temperature-sensitive alleles of yeast essential genes in the context of variation from ten different natural genetic backgrounds and map the modifiers for 19 combinations. Altogether, fitness defects for 149 of the 580 tested genes (26%) could be suppressed by genetic variation in at least one yeast strain. Suppression was generally driven by gain-of-function of a single, strong modifier gene, and involved both genes encoding complex or pathway partners suppressing specific temperature-sensitive alleles, as well as general modifiers altering the effect of many alleles. The emerging frequency of suppression and range of possible mechanisms suggest that a substantial fraction of monogenic diseases could be managed by modulating other gene products.

Immunomodulatory effect of intracellular polysaccharide from mycelia of Agaricus bitorquis (QuéL.) Sacc. Chaidam by TLR4-mediated MyD88 dependent signaling pathway.

Agaricus bitorquis (QuéL.) Sacc. Chaidam is a valuable edible fungus in Qinghai-Tibet plateau and ABSP is a novel intracellular polysaccharide from its mycelia. GC and NMR analysis determined ABSP is galactoglucomannan-like polysaccharide that may have immunomodulatory effect. This study used RAW264.7 as model cell to determine immunomodulatory effect of ABSP. After ABSP treatment, viability and phagocytic ability promoted, and NO, ROS, TNF-α levels also raised which proved ABSP had immune regulation to RAW264.7. WB and qRT-PCR determined the key proteins and genes expression of TLR4, MyD88, TRAF-6 and NF-κB significantly increased while protein and gene expression of TRAM had no significant increase. Also, TNF-α level extremely decreased by adding inhibitors of TLR4 and MyD88 which confirmed ABSP could immunologically regulate RAW264.7 byTLR4-MyD88 dependent pathway. This study would provide theoretical basis for further study on ABSP and be helpful for development of beneficial functionally foods and exploitation of this resource.

Effects of Ball Milling Combined With Cellulase Treatment on Physicochemical Properties and in vitro Hypoglycemic Ability of Sea Buckthorn Seed Meal Insoluble Dietary Fiber.

To improve the rough texture and hypoglycemic ability of sea buckthorn insoluble dietary fiber (IDF), a novel combined modification method was developed in this study. The IDF was treated with ball milling and cellulase treatment to obtain co-modified insoluble dietary fiber (CIDF). The physicochemical and functional properties of IDF, milled insoluble dietary fiber (MIDF), and CIDF were studied. After treatments, MIDF had smaller particle sizes and a looser structure, and CIDF exhibited a wrinkled surface and sparse porous structure according to scanning electron microscopy (SEM) and X-ray diffraction. Compared to IDF, MIDF and CIDF showed improved water-holding, oil-binding, and swelling capacities, improved by 16.13, 14.29, and 15.38%, and 38.5, 22.2, and 25.0%, for MIDF and CIDF, respectively. The cation exchange ability of modified samples showed improvement as well. Treatments also changed the fluidity of MIDF and CIDF. Due to the smaller particles and increased stacking, the bulk density (BD) and angle of repose of MIDF improved by 33.3% and 4.1° compared to IDF, whereas CIDF had a looser structure and thus decreased by 7.1% and 13.3° with increased fluidity. Moreover, the modification also enhanced the effects of CIDF on glucose adsorption, glucose diffusion inhibition, starch digestion inhibition, starch pasting interference, and α-amylase activity inhibition. In summary, IDF modified by ball milling combined with cellulose treatment could be developed as a functional ingredient for regulating glucose content.

Exploring genetic suppression interactions on a global scale.

Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations,in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population. These findings allow us to formulate and quantify general mechanisms of genetic suppression.

IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline.

Alzheimer's disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of ß-amyloid (Aß) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aß levels and amyloid plaque deposition by promoting the recruitment and Aß phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1ß, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

Biphasic assembly of the contractile apparatus during the first two cell division cycles in zebrafish embryos.

The large and optically clear embryos of the zebrafish provide an excellent model system in which to study the dynamic assembly of the essential contractile band components, actin and myosin, via double fluorescent labelling in combination with confocal microscopy. We report the rapid appearance (i.e. within <2 min) of a restricted arc of F-actin patches along the prospective furrow plane in a central, apical region of the blastodisc cortex. These patches then fused with each other end-to-end forming multiple actin cables, which were subsequently bundled together forming an F-actin band. During this initial assembly phase, the F-actin-based structure did not elongate laterally, but was still restricted to an arc extending ~15° either side of the blastodisc apex. This initial assembly phase was then followed by an extension phase, where additional F-actin patches were added to each end of the original arc, thus extending it out to the edges of the blastodisc. The dynamics of phosphorylated myosin light chain 2 (MLC2) recruitment to this F-actin scaffold also reflect the two-phase nature of the contractile apparatus assembly. MLC2 was not associated with the initial F-actin arc, but MLC2 clusters were recruited and assembled into the extending ends of the band. We propose that the MLC2-free central region of the contractile apparatus acts to position and then extend the cleavage furrow in the correct plane, while the actomyosin ends alone generate the force required for furrow ingression. This biphasic assembly strategy may be required to successfully divide the early cells of large embryos.

Characterization of Ca(2+) signaling in the external yolk syncytial layer during the late blastula and early gastrula periods of zebrafish development.

Preferential loading of the complementary bioluminescent (f-aequorin) and fluorescent (Calcium Green-1 dextran) Ca(2+) reporters into the yolk syncytial layer (YSL) of zebrafish embryos, revealed the generation of stochastic patterns of fast, short-range, and slow, long-range Ca(2+) waves that propagate exclusively through the external YSL (E-YSL). Starting abruptly just after doming (~4.5h post-fertilization: hpf), and ending at the shield stage (~6.0hpf) these distinct classes of waves propagated at mean velocities of ~50 and ~4µm/s, respectively. Although the number and pattern of these waves varied between embryos, their initiation site and arcs of propagation displayed a distinct dorsal bias, suggesting an association with the formation and maintenance of the nascent dorsal-ventral axis. Wave initiation coincided with a characteristic clustering of YSL nuclei (YSN), and their associated perinuclear ER, in the E-YSL. Furthermore, the inter-YSN distance (IND) appeared to be critical such that Ca(2+) wave propagation occurred only when this was <~8µm; an IND >~8µm was coincidental with wave termination at shield stage. Treatment with the IP3R antagonist, 2-APB, the Ca(2+) buffer, 5,5'-dibromo BAPTA, and the SERCA-pump inhibitor, thapsigargin, resulted in a significant disruption of the E-YSL Ca(2+) waves, whereas exposure to the RyR antagonists, ryanodine and dantrolene, had no significant effect. These findings led us to propose that the E-YSL Ca(2+) waves are generated mainly via Ca(2+) release from IP3Rs located in the perinuclear ER, and that the clustering of the YSN is an essential step in providing a CICR pathway required for wave propagation. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.

Reconstruction of crashes involving injured child occupants: the risk of serious injuries associated with sub-optimal restraint use may be reduced by better controlling occupant kinematics.

OBJECTIVE: To determine whether injuries to sub-optimally restrained child occupants in real-world crashes were likely to be preventable by alternative restraint usage practices and to assess the usefulness of crash reconstruction for exploring injury mechanisms in child occupants. METHODS: Real-world crashes in which child occupants sustained significant injuries were reconstructed on a laboratory crash sled using the Hybrid III family of child dummies. Alternative restraint scenarios and cases in which children were not seriously injured were also simulated to compare dummy kinematics and dynamic responses in optimal restraint configurations. RESULTS: Restraint misuse was associated with greater motion of the dummy torso and head during crashes, often allowing contact between the child and the vehicle interior, resulting in injury. Poor pre-crash posture for a child inappropriately restrained in an adult belt appeared to worsen the geometry of the sash (shoulder) belt, resulting in a cervical injury due to direct interaction with the belt. Dynamic dummy data did not appear to discriminate between injury and non-injury cases. CONCLUSIONS: Dummy kinematics suggest that injuries in which inappropriate use and misuse were a factor were less likely if the most appropriate restraint was used correctly. Adequately controlling the head and upper body of the child occupant was seen to prevent undesirable interactions with the vehicle interior and restraint system, which were associated with injury in the real world. Neck forces and moments and injury criteria calculated from these did not predict injury reliably.