Dioscin integrates regulation of monosaturated fatty acid metabolism to extend the life span through XBP-1/SBP-1 dependent manner.

Delay aging, especially in healthy life extension, brought the most interest to the medical field. Searching for anti-aging drugs with relative safety profiles bring natural products in hotspot. In this study, we find that dioscin promotes the health span extension in wild-type Caenorhabditis elegans. Through the genetic screening in C. elegans, we further reveal that dioscin activates the transcription factor SBP-1/SREBP by the UPRER transcription factor XBP-1 to upregulate transcription of the Δ9 desaturase FAT-5 and FAT-7, resulting in increased monounsaturated fatty acid content which requires for healthy life span extension. Intriguingly, through tissue-specific knockdown, we find that dioscin modulates the health span by activating SBP-1 in the intestine. Unexpectedly, dietary supplementation of POA and OA rescues XBP-1, SBP-1 mutants-induced shortened life span phenotype. Considering the conservation of MUFAs metabolism, dioscin may promote health span in other species, including mammals. Our work suggests that dioscin might be a promising candidate for developing anti-aging agent.

Sanguinarine promotes healthspan and innate immunity through a conserved mechanism of ROS-mediated PMK-1/SKN-1 activation.

The longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend lifespan by targeting pathways with a defined role in the aging process. Sanguinarine (San) is a benzophenanthridine alkaloid that exerts a broad spectrum of properties. In this study, we utilized Caenorhabditis elegans to examine the mechanisms by which sanguinarine influences aging and innate immunity. We find that 0.2 µM sanguinarine extends healthspan in C. elegans. We further show that sanguinarine generates reactive oxygen species (ROS), which is followed by the activation of PMK-1/SKN-1pathway to extend healthspan. Intriguingly, sanguinarine increases resistance to pathogens by reducing the bacterial burden in the intestine. In addition, we also find that sanguinarine enhances innate immunity through PMK-1/SKN-1 pathway. Our data suggest that sanguinarine may be a viable candidate for the treatment of age-related disorders.

Secondary Metabolites from Marine Micromonospora: Chemistry and Bioactivities.

Marine Micromonospora was revealed to be a rather untapped and a rich source of chemically diverse and unique bioactive natural products. This review is aimed to make a comprehensive survey of secondary metabolites that were derived from marine Micromonospora including chemical diversity and biological activities. A total of 116 compounds from 41 marine Micromonospora species have been reported, covering the literatures from 1997 to 2019. These compounds contain several structural classes such as polyketides (PKS), nonribosomal peptides (NRPS), PKS-NRPS hybrids, terpenes and others, and they present cytotoxic, antibacterial, antiparasitic, chemopreventive or antioxidant activities.

Simultaneous Correction of Complex Secondary Deformities of Cleft Lip Using Autogenous Costal Cartilage Combined With Rib Grafts.

OBJECTIVE: Complex secondary deformities of cleft lip include nasal and labial deformities, alveolar cleft, oronasal fistula, and so on. In this report, the authors present a method to simultaneously repair the above complex deformities with autogenous costal cartilage and rib grafts. METHODS: The surgical procedure of simultaneous correction includes RESULTS:: Satisfactory outcomes were achieved in all 22 patients. Fifteen patients were followed up for 6 to 24 months and exhibited good nasal shape, repaired alveolar cleft, improved labial shape, and closed oronasal fistula. Three patients presented with red nasal tips. One patient had local infection, which was cured by antibiotics. CONCLUSION: This methodAs this method has led to positive outcomes, it has the potential to be widely used in clinical practice.

Testosterone-cortisol dissociation in children exposed to prenatal maternal stress, and relationship with aggression: Project Ice Storm.

Prenatal maternal stress (PNMS) has been associated with postnatal behavioral alterations that may be partly explained by interactions between the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Yet it remains unclear whether PNMS leads to enduring HPA-HPG alterations in the offspring, and whether HPA-HPG interactions can impact behavior during development, in particular levels of aggression in childhood. Here we investigated the relationship between a marker for HPG axis function (baseline testosterone) and a marker for HPA axis response (cortisol area under the curve) in 11½-year-olds whose mothers were exposed to the 1998 Quebec ice storm during pregnancy (n = 59 children; 31 boys, 28 girls). We examined (a) whether the degree of objective or subjective PNMS regulates the testosterone-cortisol relationship at age 11½, and (b) whether this testosterone-cortisol relationship is associated with differences in aggressive behavior. We found that, at lower levels of subjective PNMS, baseline testosterone and cortisol reactivity were positively correlated; in contrast, there was no relationship between these hormones at higher levels of subjective PNMS. Cortisol response moderated the relationship between testosterone and aggression. These results support the notion PNMS may explain variance in fetal HPA-HPG interactions, and that these interactions may be associated with aggressive behavior in late childhood.

New Application of Psoralen and Angelicin on Periodontitis With Anti-bacterial, Anti-inflammatory, and Osteogenesis Effects.

Psoralen and angelicin are two effective compounds isolated from psoraleae, a traditional Chinese medicine. They have a wide range of applications for bone disease treatment and immune modulation. In this study, we explored their new applications for the treatment of periodontal diseases. This study aimed to investigate the effects of psoralen and angelicin on Porphyromonas gingivalis growth and P. gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation, and further to evaluate their effects on osteogenesis. Finally, the effects of angelicin on a mouse model of periodontitis were also investigated. The results showed that psoralen and angelicin had beneficial dose-dependent effects regarding the inhibition of planktonic P. gingivalis and biofilms of P. gingivalis. There were no significant differences in the viability of monocyte-like THP-1 cells and human periodontal ligament cells (hPDLCs) treated with either psoralen or angelicin compared to the untreated control cells. Psoralen and angelicin also markedly decreased the mRNA expression and release of inflammatory cytokines (interleukin [IL]-1ß and IL-8) by THP-1 cells in a dose-dependent manner. They significantly enhanced the alkaline phosphatase (ALP) activity of hPDLCs and up-regulated the expression of osteogenic proteins (runt-related transcription factor 2 [RUNX2], distal-less homeobox 5 [DLX5], and osteopontin [OPN]). Angelicin significantly attenuated alveolar bone loss and inflammation response in the mice with periodontitis. In conclusion, our data demonstrated that psoralen and angelicin could inhibit the growth of planktonic P. gingivalis and P. gingivalis biofilm. It is also the first report on the anti-inflammatory effect of psoralen and angelicin against Pg-LPS. They also had an osteogenesis-potentiating effect on hPDLCs. The in vivo study also indicated the effect of angelicin regarding protection against periodontitis. Our study highlighted the potential ability of psoralen and angelicin to act as novel natural agents to prevent and treat periodontitis.

Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice.

BACKGROUND: Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) is one of the major pathogenic factors of chronic periodontitis (CP). Few reports on the correlation between P. gingivalis-LPS and cognitive function exist. Thus, the present study aimed to investigate the effects of P. gingivalis-LPS on cognitive function and the associated underlying mechanism in C57BL/6 mice. METHODS: The C57BL/6 mice were injected with P. gingivalis-LPS (5 mg kg-1) either with or without Toll-like receptor 4 (TLR4) inhibitor (TAK-242, 5 mg kg-1). After 7 days, behavioral alterations were assessed with the open field test (OFT), Morris water maze (MWM) test, and passive avoidance test (PAT). The activation of astrocytes and microglia in the cerebral cortex and hippocampus of mice was observed by immunohistochemistry. The expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8), TLRs (TLR2, TLR3, and TLR4), and CD14 and the activation of the NF-κB signaling pathway (IRAK1, p65, and p-p65) in the cerebral cortex of the mice were evaluated by RT-PCR, ELISA, and western blot. RESULTS: The OFT showed that P. gingivalis-LPS did not affect the initiative and activity of mice. Administration of P. gingivalis-LPS significantly impaired spatial learning and memory during the MWM test and attenuated the ability of passive avoidance learning during the PAT. Both astrocytes and microglia were activated in the cortex and hippocampus. The messenger RNA (mRNA) and protein expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8) was upregulated by P. gingivalis-LPS in the cortex. In addition, the TLR4/NF-κB signaling pathway was activated (TLR4, CD14, IRAK1, and p-p65). These effects were effectively alleviated by TAK-242. CONCLUSIONS: Administration of P. gingivalis-LPS can lead to learning and memory impairment in C57BL/6 mice. This impairment is mediated by activation of the TLR4 signaling pathway. Our study suggests that P. gingivalis-LPS-induced neuroinflammation plays an important role in cognitive impairment. It also reveals that endotoxins of periodontal pathogens could represent a risk factor for cognitive disorders.

Hesperidin induces apoptosis and G0/G1 arrest in human non-small cell lung cancer A549 cells.

Lung cancer has high incidence and mortality rates worldwide. In the present study, the mechanisms by which hesperidin decreases the viability and induces the apoptosis of human non-small cell lung cancer (NSCLC) A549 cells were investigated. Initially, MTT and flow cytometric assays were performed to evaluate the effects of hesperidin on the viability and apoptosis of A549 cells and human normal lung epithelial BEAS-2B cells. The results revealed that hesperidin has no negative effects on the human normal lung epithelial BEAS-2B cells and the viability of cells treated with various concentrations of hesperidin was inhibited in a time- and dose-dependent manner compared with the control groups. Subsequently, the expression levels of proteins involved in the mitochondria-associated apoptotic pathway were studied by western blot analysis. Hesperidin was identified to induce A549 cell apoptosis by downregulating the levels of B-cell lymphoma-2 (Bcl-2) and Bcl extra large protein and simultaneously upregulating the levels of Bcl-2-associated X protein, BH3 interacting-domain death agonist (Bid), tBid, cleaved caspase-9, cleaved caspase-3 and cleaved poly(adenosine diphosphate ribose)polymerase. The effect of hesperidin on the cell cycle was assessed by flow cytometry. Hesperidin was observed to cause G0/G1 arrest of A549 cells by decreasing the expression of cyclin D1 and increasing the expression of p21 and p53. In summary, it was demonstrated that hesperidin induced apoptosis through the mitochondrial apoptotic pathway and induced G0/G1 arrest in human NSCLC A549 cells. Therefore, hesperidin may be developed as a potential therapeutic drug for the treatment of NSCLC.

[Knockdown of DNA-PKcs inhibits cell cycle and its mechanism of drug-resistant Bel7402/5-Fu hepatocellular carcinoma cells].

Objective To study the effect of the knock-down of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on the cell cycle of the multidrug-resistant (MDR) Bel7402/5-Fu hepatocellular carcinoma cells and its MDR mechanism. Methods After cationic liposome-mediated siDNA-PKcs oligonucleotide transfection, the drug sensitivity of Bel7402/5-Fu cells to 5-fluorouracil (5-Fu) and adriamycin (ADM) was determined by MTT assay; the cell cycle were detected by flow cytometry; meanwhile, the protein expressions of cell cycle-related proteins P21, cell cycle protein B1 (cyclin B1), cell cycle division protein 2 (CDC2) were tested by Western blotting; the expressions of ataxia telangiectasia mutated (ATM) and p53 at both mRNA and protein levels were detected by real-time PCR and Western blot analysis. Results The MTT results showed siDNA-PKcs increased the chemotherapeutic sensitivity of Bel7402/5-Fu cells to 5-Fu and ADM. The flow cytometric analysis showed siDNA-PKcs decreased the percentage of S-phase cells but increased the percentage of G2/M phase cells. Western blotting showed siDNA-PKcs increased the protein expression of P21 but decreased cyclinB1 and CDC2 proteins. In addition, siDNA-PKcs also increased the expressions of ATM and p53. Conclusion DNA-PKcs silencing increases P21 while decreases cyclin B1 and CDC2 expressions, and finally induces G2/M phase arrest in Bel7402/5-Fu cells, which may be related to ATM-p53 signaling pathway.

Peritraumatic Distress Mediates the Effect of Severity of Disaster Exposure on Perinatal Depression: The Iowa Flood Study.

Disaster exposure during pregnancy has received limited attention. This study examined the impact of the 2008 Iowa Floods on perinatal maternal depression and well-being, and the role of peritraumatic distress as a possible mechanism explaining this link. Perinatal women (N = 171) completed measures of depressive symptoms and general well-being at 5 timepoints from pregnancy to 30 months postpartum. Objectively assessed prenatal flood exposure was associated with greater depression (r = .15). Further, flood-related peritraumatic distress was uniquely associated with greater depression (r = .23), and was a key mechanism through which flood exposure led to depression. Prenatal flood exposure was also associated with general well-being (r = .18); however, a mechanism other than peritraumatic distress appears to have been responsible for the effect of flood exposure on well-being. We discuss the implications of these findings for informing etiological models and enhancing the efficacy of interventions for maternal psychopathology.

Partner support and maternal depression in the context of the Iowa floods.

A systematic investigation of the role of prenatal partner support in perinatal maternal depression was conducted. Separate facets of partner support were examined (i.e., received support and support adequacy) and a multidimensional model of support was applied to investigate the effects of distinct types of support (i.e., informational, physical comfort, emotional/esteem, and tangible support). Both main and stress-buffering models of partner support were tested in the context of prenatal maternal stress resulting from exposure to a natural disaster. Questionnaire data were analyzed from 145 partnered women using growth curve analytic techniques. Results indicate that received support interacts with maternal flood stress during pregnancy to weaken the association between stress and trajectories of maternal depression from pregnancy to 30 months postpartum. Support adequacy did not interact with stress, but was associated with levels of depressive symptoms controlling for maternal stress and received support. Results demonstrate the distinct roles of various facets and types of support for a more refined explanatory model of prenatal partner support and perinatal maternal depression. Results inform both main effect and stress buffering models of partner support as they apply to the etiology of perinatal maternal depression, and highlight the importance of promoting partner support during pregnancy that matches support preferences.

Brief communication: prenatal and early postnatal stress exposure influences long bone length in adult rat offspring.

Stress during the prenatal and early postnatal periods (perinatal stress, PS) is known to impact offspring cognitive, behavioral, and physical development, but effects on skeletal growth are not clear. Our objective was to analyze effects of variable, mild, daily PS exposure on adult offspring long bone length. Twelve pregnant rat dams were randomly assigned to receive variable stress from gestational days 14-21 (Prenatal group), postpartum days 2-9 (Postnatal), both periods (Pre-Post), or no stress (Control). Differences in adult offspring tibia and femur length were analyzed among treatment groups. Mean tibia length differed among groups for males (P = 0.016) and females (P = 0.009), and differences for femur length approached significance for males (P = 0.051). Long bone length was shorter among PS-exposed offspring, especially those exposed to postnatal stress (Postnatal and Pre-Post groups). Results persisted when controlling for nose-tail length. These differences might reflect early stunting that is maintained in adulthood, or delayed growth among PS-exposed offspring. This study suggests that PS results in shorter long bones in adulthood, independently of effects on overall body size. Stunting and growth retardation are major global health burdens. Our study adds to a growing body of evidence suggesting that PS is a risk factor for poor linear growth.